Flu vaccine - AbsoluteAstronomy.com

"Flu shot" redirects here. For the 30 Rock episode, see Flu Shot (30 Rock)
Flu Shot (30 Rock)
"Flu Shot" is the eighth episode of the third season of the American television comedy series 30 Rock. It was written by Jon Pollack, and directed by series producer Don Scardino. The episode originally aired on the National Broadcasting Company in the United States on January 15, 2009...

The influenza vaccine, also known as flu shot, is an annual vaccine

Vaccine

A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...

to protect against the highly variable influenza virus. Each injected seasonal influenza vaccine contains three influenza viruses: one influenza type A subtype H3N2 virus strain, one influenza type A subtype H1N1 (seasonal) virus strain, and one influenza type B virus strain.

Purpose and benefits of annual flu vaccination

"Influenza vaccination is the most effective method for preventing influenza virus infection and its potentially severe complications."

Deadly epidemics each winter

An influenza epidemic emerges during flu season

Flu season

Flu season is a annually-recurring time period characterized by the prevalence of outbreaks of influenza . The season occurs during the cold half of the year in each hemisphere. Influenza activity can sometimes be predicted and even tracked geographically...

each winter. There are two flu seasons annually, corresponding to the occurrence of winter in opposite months in the Northern and Southern Hemispheres.

Worldwide, seasonal influenza kills an estimated 250,000 to 500,000 people each year. Tens of thousands of Americans die in a typical flu season, but there are notable variations from year to year. In 2010 the Centers for Disease Control and Prevention

Centers for Disease Control and Prevention

The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...

(CDC) in the United States

United States

The United States of America is a federal constitutional republic comprising fifty states and a federal district...

changed the way it reports the 30-year estimates for deaths from influenza. Now they are reported as a range from a low of about 3,300 deaths to a high of 49,000 per year over the past 30 years.

The majority of deaths in the industrialized world occur in adults aged 65 and over.
A review at the NIAID division of the NIH in 2008 concluded that "Seasonal influenza causes more than 200,000 hospitalizations and 41,000 deaths in the U.S. every year, and is the seventh leading cause of death in the U.S." The average total economic costs caused by the annual influenza

Influenza

Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...

outbreak in the U.S. have been estimated at over $80 billion.

The number of annual influenza-related hospitalizations is many times the number of deaths. "The high costs of hospitalizing young children for influenza creates a significant economic burden in the United States, underscoring the importance of preventive flu shots for
children and the people with whom they have regular contact..."

In 2006 the United States began recommending influenza vaccinations for preschoolers but Canada did not follow suit until 2010, "thereby creating a natural experiment to evaluate the effect of the policy in the United States."

A Canadian study found emergency room visits significantly lower for 2- to 4-year-olds in Boston than in Montreal through the period (34% fewer ER trips). Vaccination of preschoolers may have reduced their likelihood of transmission of flu to older siblings and raised the chances that their parents would vaccinate older children as well, since there were also 18 percent fewer emergency room visits by 5- to 18-year-olds in Boston than Montreal during the study period.

In another six-year observational study, vaccination of children aged 6 months through 5 years was found to prevent illness in more than half.

National advice on flu vaccination

In Canada, the National Advisory Committee on Immunization, the group that advises the Public Health Agency of Canada

Public Health Agency of Canada

The Public Health Agency of Canada is an agency of the Government of Canada that is responsible for public health, emergency preparedness, and response and infectious and chronic disease control and prevention...

, currently recommends that everyone aged 2 to 64 years be encouraged to receive annual influenza vaccination, and that children between the age of six and 24 months, and their household contacts, should be considered a high priority for the flu vaccine.

In the United States, "Routine influenza vaccination is recommended for all persons aged ≥6 months." The sole group for whom routine influenza vaccination is still not recommended is infants less than six months of age.

Within its blanket recommendation for general vaccination, the United States, the Centers for Disease Control and Prevention

Centers for Disease Control and Prevention

(CDC) emphasizes to clinicians the special urgency of vaccination for members of certain vulnerable groups, and their caregivers:

Vaccination is especially important for people at higher risk of serious influenza complications or people who live with or care for people at higher risk for serious complications.

Benefits of vaccination

According to research published in July 2010, vaccination against influenza is also thought to be important for members of high-risk groups who would be likely to suffer complications from influenza, for example pregnant women and children and teenagers from six months to 18 years of age;

In expanding the new upper age limit to 18 years, the aim is to reduce both the time children and parents lose from visits to pediatricians and missing school and the need for antibiotics for complications

An added expected benefit would be indirect — to reduce the number of influenza cases among parents and other household members, and possibly spread to the general community.

Vaccination of school-age children has a strong protective effect on the adults and elderly with whom the children are in contact. Children born to mothers who received flu vaccination while pregnant are strongly protected from having to be hospitalized with the flu. "The effectiveness of influenza vaccine given to mothers during pregnancy in preventing hospitalization among their infants, adjusted for potential confounders, was 91.5%."

Healthy, working adults who received influenza vaccine reported 25 percent fewer episodes of upper respiratory illness than those who received the placebo (105 vs. 140 episodes per 100 subjects, P < 0.001), 43 percent fewer days of sick leave from work due to upper respiratory illness (70 vs. 122 days per 100 subjects, P = 0.001), and 44 percent fewer visits to physicians' offices for upper respiratory illnesses (31 vs. 55 visits per 100 subjects, P = 0.004). The study, reported in the NEJM, estimated cost savings at $46.85 per person vaccinated, and concluded that "Vaccination against influenza has substantial health-related and economic benefits for healthy, working adults." PMID 7666874

Influenza vaccination has been shown highly effective in health care workers, with minimal adverse effects. In a study of forty matched nursing homes, staff influenza vaccination rates were 69.9% in the vaccination arm versus 31.8% in the control arm. The vaccinated staff experienced a 42% reduction in sick leave from work (P=.03). A review of eighteen studies likewise found a strong net benefit to health care workers. The two of these eighteen studies that assessed the relationship of patient mortality relative to staff influenza vaccine uptake both found that higher rates of health care worker vaccination correlated with reduced patient deaths. An analysis of data and patient population health in New Mexico's 75 long-term care facilities nursing homes found that as vaccination rates of health care personnel with direct patient contact rose from 51 to 75 percent, the chances of a flu outbreak among patients in that facility went down by 87 percent. The New Mexico study showed that vaccinating health care personnel provided more protection to residents than vaccinating the residents themselves.

In a 2010 survey of healthcare workers, 63.5% reported that they received the flu vaccine during the 2010-11 season, an increase from 61.9% reported the previous season. Health professionals with direct patient contact had higher vaccination uptake, such as physicians and dentists (84.2%) and nurse practitioners (82.6%).

Cross-protection

Annual seasonal flu vaccination may provide some level of protection against novel flu viruses.
A number of studies suggest that seasonal flu vaccine may offer cross-protection, both against the H5N1

H5N1

Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...

-type (avian influenza) H5N1 infection

Transmission and infection of H5N1

Transmission and infection of H5N1 from infected avian sources to humans is a concern due to the global spread of H5N1 that constitutes a pandemic threat....

and the 2009 flu pandemic

2009 flu pandemic

The 2009 flu pandemic was an influenza pandemic, and the second of the two pandemics involving H1N1 influenza virus , albeit in a new version...

(the H1N1 "swine flu.") Vaccine protection can be long-lasting. Participants who received vaccination against the swine flu in 1976 still enjoyed benefits 33 years later, exhibiting a significantly enhanced immune response to the 2009 pandemic H1N1.

History of the flu vaccine

Vaccines are used in both humans and nonhumans. Human vaccine is meant unless specifically identified as a veterinary, poultry or livestock vaccine.

Influenza

The first influenza pandemic

Influenza pandemic

An influenza pandemic is an epidemic of an influenza virus that spreads on a worldwide scale and infects a large proportion of the human population. In contrast to the regular seasonal epidemics of influenza, these pandemics occur irregularly, with the 1918 Spanish flu the most serious pandemic in...

was recorded in 1580; since this time, various methods have been employed to eradicate its cause. The etiological cause of influenza, the orthomyxoviridae was finally discovered by the Medical Research Council

Medical Research Council (UK)

The Medical Research Council is a publicly-funded agency responsible for co-ordinating and funding medical research in the United Kingdom. It is one of seven Research Councils in the UK and is answerable to, although politically independent from, the Department for Business, Innovation and Skills...

(MRC) of the United Kingdom

United Kingdom

The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...

in 1933.

Known flu pandemics:

1889–90 — Asiatic (Russian) Flu, mortality rate said to be 0.75–1 death per 1000 possibly H2N2
H2N2
H2N2 is a subtype of the type influenzavirus A. H2N2 has mutated into various strains including the Asian flu strain , H3N2, and various strains found in birds...
1900 — Possibly H3N8
H3N8
H3N8 is a subtype of the species Influenza A virus that is endemic in birds, horses and dogs.-Introduction:Equine influenza is a highly contagious respiratorydisease of horses and related animals such as donkeys,...
1918–20 – Spanish Flu
Spanish flu
The 1918 flu pandemic was an influenza pandemic, and the first of the two pandemics involving H1N1 influenza virus . It was an unusually severe and deadly pandemic that spread across the world. Historical and epidemiological data are inadequate to identify the geographic origin...

, 500 million ill, at least 20–40 million died of H1N1
H1N1
'Influenza A virus is a subtype of influenza A virus and was the most common cause of human influenza in 2009. Some strains of H1N1 are endemic in humans and cause a small fraction of all influenza-like illness and a small fraction of all seasonal influenza. H1N1 strains caused a few percent of...
1957–58 – Asian Flu
Asian flu
Asian Flu may refer to:* The Asian Financial Crisis of 1997, or* Asian Flu, the H2N2 virus...

, 1 to 1.5 million died of H2N2
H2N2
H2N2 is a subtype of the type influenzavirus A. H2N2 has mutated into various strains including the Asian flu strain , H3N2, and various strains found in birds...
1968–69 – Hong Kong Flu
Hong Kong flu
The Hong Kong flu was a category 2 flu pandemic whose outbreak in 1968 and 1969 killed an estimated one million people worldwide. It was caused by an H3N2 strain of the influenza A virus, descended from H2N2 through antigenic shift, a genetic process in which genes from multiple subtypes reassorted...

, 3/4 to 1 million died of H3N2
H3N2
Influenza A virus subtype H3N2 is a subtype of viruses that cause influenza . H3N2 Viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains...
2009 - Swine Flu
2009 flu pandemic
The 2009 flu pandemic was an influenza pandemic, and the second of the two pandemics involving H1N1 influenza virus , albeit in a new version...

, caused by H1N1/09
Pandemic H1N1/09 virus
The Pandemic H1N1/09 virus is a swine origin Influenza A virus subtype H1N1 virus strain responsible for the 2009 flu pandemic. For other names see the Nomenclature section below.-Virus characteristics:...

, died

Flu vaccine origins and development

In the world wide Spanish flu

Spanish flu

The 1918 flu pandemic was an influenza pandemic, and the first of the two pandemics involving H1N1 influenza virus . It was an unusually severe and deadly pandemic that spread across the world. Historical and epidemiological data are inadequate to identify the geographic origin...

pandemic of 1918, "Physicians tried everything they knew, everything they had ever heard of, from the ancient art of bleeding patients, to administering oxygen, to developing new vaccines and sera (chiefly against what we now call Hemophilus influenzae—a name derived from the fact that it was originally considered the etiological agent—and several types of pneumococci). Only one therapeutic measure, transfusing blood from recovered patients to new victims, showed any hint of success."

In 1931, viral growth in embryonated hens' eggs was reported by Ernest William Goodpasture

Ernest William Goodpasture

Dr. Ernest William Goodpasture was an American pathologist and physician. Goodpasture advanced the scientific understanding of the pathogenesis of infectious diseases, parasitism, and a variety of rickettsial and viral infections...

and colleagues at Vanderbilt University

Vanderbilt University

Vanderbilt University is a private research university located in Nashville, Tennessee, United States. Founded in 1873, the university is named for shipping and rail magnate "Commodore" Cornelius Vanderbilt, who provided Vanderbilt its initial $1 million endowment despite having never been to the...

. The work was extended to growth of influenza virus by several workers, including Thomas Frances, Wilson Smith and Macfarlane Burnet, leading to the first experimental influenza vaccines. In the 1940s, the US military developed the first approved inactivated vaccines for influenza, which were used in the Second World War. Greater advances were made in vaccinology and immunology, and vaccines became safer and mass-produced. Today, thanks to the advances of molecular technology, we are on the verge of making influenza vaccines through the genetic manipulation of influenza genes.

Flu vaccine acceptance

According to the CDC: "Influenza vaccination is the primary method for preventing influenza and its severe complications. [...] Vaccination is associated with reductions in influenza-related respiratory illness and physician visits among all age groups, hospitalization and death among persons at high risk, otitis media

Otitis media

Otitis media is inflammation of the middle ear, or a middle ear infection.It occurs in the area between the tympanic membrane and the inner ear, including a duct known as the eustachian tube. It is one of the two categories of ear inflammation that can underlie what is commonly called an earache,...

among children, and work absenteeism among adults. Although influenza vaccination levels increased substantially during the 1990s, further improvements in vaccine coverage levels are needed".

The current egg-based technology for producing influenza vaccine was created in the 1950s. In the U.S. swine flu scare of 1976

1976 swine flu outbreak

The 1976 swine flu outbreak, also known as the swine flu fiasco, or the swine flu debacle, was a strain of H1N1 influenza virus that appeared in 1976. Infections were only detected from January 19 to February 9, and were not found outside Fort Dix. The outbreak is most remembered for the mass...

, President Gerald Ford

Gerald Ford

Gerald Rudolph "Jerry" Ford, Jr. was the 38th President of the United States, serving from 1974 to 1977, and the 40th Vice President of the United States serving from 1973 to 1974...

was confronted with a potential swine flu pandemic. The vaccination

Vaccination

Vaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...

program was rushed, yet plagued by delays and public relations problems. Meanwhile, maximum military containment efforts succeeded unexpectedly in confining the new strain to the single army base where it had originated. On that base a number of soldiers fell severely ill, but only one died. The program was canceled, after about 24% of the population had received vaccinations. An excess in deaths of twenty-five over normal annual levels as well as 400 excess hospitalizations, both from Guillain-Barré syndrome

Guillain-Barré syndrome

Guillain–Barré syndrome , sometimes called Landry's paralysis, is an acute inflammatory demyelinating polyneuropathy , a disorder affecting the peripheral nervous system. Ascending paralysis, weakness beginning in the feet and hands and migrating towards the trunk, is the most typical symptom...

, were estimated to have occurred from the vaccination program itself, illustrating that vaccine itself is not free of risks. The result has been cited to stoke lingering doubts about vaccination. In the end, however, even the maligned 1976 vaccine may have saved lives. A 2010 study found a significantly enhanced immune response against the 2009 pandemic H1N1 in study participants who had received vaccination against the swine flu in 1976.

Current status

Influenza research includes molecular virology

Molecular Virology

Molecular Virology is the study of viruses at the molecular level.In particular, this includes the analysis of individual viral genes and gene products, and their interaction with host cellular proteins....

, molecular evolution

Molecular evolution

Molecular evolution is in part a process of evolution at the scale of DNA, RNA, and proteins. Molecular evolution emerged as a scientific field in the 1960s as researchers from molecular biology, evolutionary biology and population genetics sought to understand recent discoveries on the structure...

, pathogenesis

Pathogenesis

The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...

, host immune responses, genomics

Genomics

Genomics is a discipline in genetics concerning the study of the genomes of organisms. The field includes intensive efforts to determine the entire DNA sequence of organisms and fine-scale genetic mapping efforts. The field also includes studies of intragenomic phenomena such as heterosis,...

, and epidemiology

Epidemiology

Epidemiology is the study of health-event, health-characteristic, or health-determinant patterns in a population. It is the cornerstone method of public health research, and helps inform policy decisions and evidence-based medicine by identifying risk factors for disease and targets for preventive...

. These help in developing influenza countermeasures such as vaccine

Vaccine

s, therapies and diagnostic tools. Improved influenza countermeasures require basic research on how viruses enter cells, replicate, mutate, evolve into new strains and induce an immune response. The Influenza Genome Sequencing Project

Influenza Genome Sequencing Project

The Influenza Genome Sequencing Project is an American-based genome project aimed at improving the availability of genomic sequence data from influenza viruses and related information....

is creating a library of influenza sequences that will help us understand what makes one strain more lethal than another, what genetic determinants most affect immunogenicity

Immunogenicity

Immunogenicity is the ability of a particular substance, such as an antigen or epitope, to provoke an immune response in the body of a human or animal.- Immunogenicity :The ability to induce humoral and/or cell-mediated immune responses....

, and how the virus evolves over time. Solutions to limitations in current vaccine methods are being researched.

The rapid development, production, and distribution of pandemic influenza vaccines could potentially save millions of lives during an influenza pandemic. Due to the short time frame between identification of a pandemic strain and need for vaccination, researchers are looking at novel technologies for vaccine production that could provide better "real-time" access and be produced more affordably, thereby increasing access for people living in low- and moderate-income countries, where an influenza pandemic may likely originate, such as live attenuated (egg-based or cell-based) technology and recombinant technologies (proteins and virus-like particles). As of July 2009, more than 70 known clinical trials have been completed or are ongoing for pandemic influenza vaccines. In September 2009, the US Food and Drug Administration

Food and Drug Administration

The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...

approved four vaccines against the 2009 H1N1 influenza virus (the current pandemic strain), and expected the initial vaccine lots to be available within the following month.

Prospects for universal flu vaccines

Many groups world wide are working on a universal flu vaccine that will not need changing each year, as the sector has been viewed as "increasingly hot". Companies pursuing the vaccine as of 2009 and 2010 include BiondVax, Theraclone, Dynavax Technologies Corporation, VaxInnate, Crucell NV, Inovio Pharmaceuticals, and Immune Targeting Systems (ITS)

In 2008 Acambis announced work on a universal flu vaccine (ACAM-FLU-ATM) based on the less variable M2 protein component of the flu virus shell. See also H5N1 vaccines.

In 2009, the Wistar Institute

Wistar Institute

The Wistar Institute is a biomedical center, with a focus on cancer research and vaccine development. It is located in the University City section of Philadelphia, Pa...

received a patent for using "a variety of peptides" in a flu vaccine, and announced it was seeking a corporate partner.

In 2010, the National Institute of Allergy and Infectious Diseases (NIAID) of the U.S. NIH announced a breakthrough; the effort targets the stem, which mutates less often than the head of the virus.

DNA vaccines

DNA vaccination

DNA vaccination is a technique for protecting an organism against disease by injecting it with genetically engineered DNA to produce an immunological response. Nucleic acid vaccines are still experimental, and have been applied to a number of viral, bacterial and parasitic models of disease, as...

such as VGX-3400X (aimed at multiple H5N1 strains) contain DNA fragments (plasmids)
. Inovios SynCon DNA vaccines include H5N1 and H1N1 subtypes.

In July 2011, F16 researchers created an antibody

Antibody

An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...

, which targets a protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

found on the surface of all influenza A viruses called haemagglutinin. F16 is the only known antibody that treats all 16 subtypes of the influenza A virus and might be the lynchpin for a universal influenza vaccine.

Other vaccines are polypeptide based.

Some universal flu vaccines have started early stage clinical trials.

BiondVax are targeting the less variable stalk of the haemagglutinin molecule with Multimeric-001. This is aimed at type A (inc H1N1) and Type B influenza and has started a phase IIa study.
Dynavax have developed a vaccine N8295 based on two highly conserved antigens NP
Nucleoprotein
A nucleoprotein is any protein that is structurally associated with nucleic acid .Many viruses harness this protein, and they are known for being host-specific...

and M2e and their TLR9
TLR9
Toll-like receptor 9 is a protein that in humans is encoded by the TLR9 gene. TLR9 has also been designated as CD289 .- Function :...

agonist, and started clinical trials in June 2010.
ITS's fp01 includes 6 peptide antigens to highly conserved segments of the PA, PB1, PB2, NP & M1 proteins, and has started phase I trials.

Based on the results of animal studies, a universal flu vaccine may use a two-step vaccination strategy — priming with a DNA-based HA vaccine followed by a second dose with an inactivated, attenuated, or adenovirus-vector–based vaccine.

Some people given a 2009 H1N1 flu vaccine have developed broadly protective antibodies which has raised hopes for a universal flu vaccine.

Clinical trials of vaccines

A vaccine is assessed by the reduction of the risk of disease that is produced by vaccination, the vaccine's efficacy. In contrast, in the field, the effectiveness of a vaccine is the practical reduction in risk for an individual when they are vaccinated under real-world conditions. Measuring efficacy of influenza vaccines is relatively simple, as the immune response produced by the vaccine can be assessed in animal models, or the amount of antibody produced in vaccinated people can be measured, or most rigorously, by immunising adult volunteers and then challenging with virulent influenza virus. In studies such as these, influenza vaccines showed high efficacy and produced a protective immune response. For ethical reasons, such challenge studies cannot be performed in the population most at risk from influenza – the elderly and young children. However, studies on the effectiveness of flu vaccines in the real world are uniquely difficult. The vaccine may not be matched to the viruses in circulation that year; virus prevalence varies widely between years, and influenza is often confused with other influenza-like illness

Influenza-like illness

Influenza-like illness , also known as acute respiratory infection and flu-like syndrome, is a medical diagnosis of possible influenza or other illness causing a set of common symptoms, with SARI referring to Severe Acute Respiratory Infection.Symptoms commonly include fever, shivering, chills,...

es.

Nevertheless, multiple clinical trials of both live and inactivated influenza vaccines against seasonal influenza have been performed and their results pooled and analyzed in several recent meta-analyses. Studies on live vaccines have very limited data, but these preparations may be more effective than inactivated vaccines. The meta-analyses examined the efficacy and effectiveness of inactivated vaccines against seasonal influenza in adults, children, and the elderly. In adults, vaccines show high efficacy against the targeted strains, but low effectiveness overall, so the benefits of vaccination are small, with a one-quarter reduction in risk of contracting influenza but no significant effect on the rate of hospitalization. However, the risk of serious complications from influenza is small in adults, so unless the effect from vaccination is large it might not have been detected. In children, vaccines again showed high efficacy, but low effectiveness in preventing "flu-like illness". In children under two the data are extremely limited, but vaccination appeared to confer no measurable benefit. In the elderly, vaccination does not reduce the frequency of influenza, but seems to reduce pneumonia, hospital admission and deaths from influenza or pneumonia. However, the current data on the effectiveness of influenza vaccines in the elderly may be unreliable, due to high levels of selection bias

Selection bias

Selection bias is a statistical bias in which there is an error in choosing the individuals or groups to take part in a scientific study. It is sometimes referred to as the selection effect. The term "selection bias" most often refers to the distortion of a statistical analysis, resulting from the...

.

Overall, the benefit of influenza vaccination is clear in the elderly and vaccination of children may be beneficial. Routine vaccination of adults is not predicted to produce significant improvements in public health. The apparent contradiction between vaccines with high efficacy, but low effectiveness, may reflect the difficulty in diagnosing influenza under clinical conditions and the large number of strains circulating in the population. In contrast, during an influenza pandemic, where a single strain of virus is responsible for illnesses, an effective vaccine could produce a large decrease in the number of cases and be highly effective in controlling an epidemic. However, such a vaccine would have to be produced and distributed rapidly to have maximum effect.

Effectiveness of vaccine

The CDC reports that studies demonstrate that vaccination is a cost-effective counter-measure to seasonal outbreaks of influenza. However it is not perfect. A study led by Dr. David K. Shay in February, 2008 reported that

"full immunization against flu provided about a 75 percent effectiveness rate in preventing hospitalizations from influenza complications in the 2005-6 and 2006-7 influenza seasons."

Influenza vaccine has been demonstrated to prevent disease and death, both in numerous controlled studies and in painstaking scientific reviews of these studies. However the rigor of the science of these studies has also been criticized. A 2006 Cochrane review of influenza vaccination in the elderly stated "The apparent high effectiveness of the vaccines in preventing death from all causes may reflect a baseline imbalance in health status and other systematic differences in the two groups of participants. In one observational study, a sharply lower risk of death or hospitalization for pneumonia was seen in vaccinated persons:

Results: The relative risk of death for vaccinated persons compared with unvaccinated persons was 0.39 [95% confidence interval (95% CI), 0.33-0.47] before influenza season, 0.56 (0.52-0.61) during influenza season, and 0.74 (0.67-0.80) after influenza season. The relative risk of pneumonia hospitalization was 0.72 (0.59-0.89) before, 0.82 (0.75-0.89) during, and 0.95 (0.85-1.07) after influenza season. Adjustment for diagnosis code variables resulted in estimates that were further from the null, in all time periods.

A better vitality and lower pneumonia hospitalization was thus observed in the vaccinated group in this non-randomized population study before, during, and after influenza season. This could, however, have been ascribed in whole or in part to self-selection bias, since vaccinated persons were already healthier before flu season. Some sub-populations have been assumed to benefit from vaccination in the absence of directly specific studies. For example, a 2008 Cochrane review of healthy children found "Influenza vaccines are efficacious in children older than two but little evidence is available for children under two.". The CDC in 2010, after a review of extant studies, extended its guidelines to recommend that every child over 6 months be given the influenza vaccine. Vaccines were shown effective against the influenza strains they are designed to protect against, but this translated to only a modest impact on working days lost due to influenza-like infections in a 2007 Cochrane review on influenza vaccines in healthy adults.
While a 2010 Cochrane review noted that "Influenza vaccines have a modest effect in reducing influenza symptoms and working days lost" it stated found no evidence of prevention of complications, such as pneumonia, or transmission.

The group most vulnerable to non-pandemic flu, the elderly, is also the least benefitted by the vaccine, with an average efficacy rate ranging from 40-50% at age 65, and only 15-30% past age 70. There are multiple reasons behind this steep decline in vaccine efficacy, the most common of which are the declining immunological function and frailty associated with advanced age. An influenza vaccine with four times the usual amount of antigen (Fluzone High Dose) has shown increased immune response in the elderly and has now been approved by the U.S. Food and Drug Administration

Food and Drug Administration

The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...

(FDA).

In a non-pandemic year, a person in the United States aged 50–64 is nearly ten times more likely to die an influenza-associated death than a younger person, and a person over age 65 is over ten times more likely to die an influenza-associated death than the 50–64 age group. Vaccination of those over age 65 reduces influenza-associated death by about 50%. However, it is unlikely that the vaccine completely explains the results since elderly people who get vaccinated are probably more healthy and health-conscious than those who do not. Elderly participants randomized to a high-dose group (60 micrograms) had antibody levels 44 to 79 percent higher than did those who received the normal dose of vaccine. Elderly volunteers receiving the higher dose were more likely to achieve protective levels of antibody.

As mortality is also high among infants who contract influenza, the household contacts and caregivers of infants should be vaccinated to reduce the risk of passing an influenza infection to the infant. Data from the years when Japan required annual flu vaccinations for school-aged children indicate that vaccinating children—the group most likely to catch and spread the disease—has a strikingly positive effect on reducing mortality among older people: one life saved for every 420 children who received the flu vaccine. This may be due to herd immunity

Herd immunity

Herd immunity describes a form of immunity that occurs when the vaccination of a significant portion of a population provides a measure of protection for individuals who have not developed immunity...

or to direct causes, such as individual older people not being exposed to influenza. For example, retired grandparents often risk infection by caring for their sick grandchildren in households where the parents can't take time off work or are sick themselves.

In most years (16 of the 19 years before 2007), the flu vaccine strains have been a good match for the circulating strains. In other flu seasons like that of 2007/2008, the match was less useful. But even a mis-matched vaccine can often provide some protection:

...[A]ntibodies made in response to vaccination with one strain of influenza viruses can provide protection against different, but related strains. A less than ideal match may result in reduced vaccine effectiveness against the variant viruses, but it still can provide enough protection to prevent or lessen illness severity and prevent flu-related complications. In addition, it's important to remember that the influenza vaccine contains three virus strains so the vaccine can also protect against the other two viruses. For these reasons, even during seasons when there is a less than ideal match, CDC continues to recommend influenza vaccination. This is particularly important for people at high risk for serious flu complications and their close contacts.

Comparing flu shot to nasal spray

Flu vaccines are available either as

TIV (flu shot (injection
Injection (medicine)
An injection is an infusion method of putting fluid into the body, usually with a hollow needle and a syringe which is pierced through the skin to a sufficient depth for the material to be forced into the body...

) of trivalent (three strains; usually A/H1N1, A/H3N2, and B) inactivated (killed) vaccine) or
LAIV (nasal spray (mist) of live attenuated influenza vaccine
Live attenuated influenza vaccine
Live attenuated influenza vaccine is a type of influenza vaccine. It is an attenuated vaccine. This is in contrast to most influenza vaccines, which are inactivated vaccines. Both forms of vaccine are typically trivalent...

.)

TIV works by putting into the bloodstream those parts of three strains of flu virus that the body uses to create antibodies; while LAIV works by inoculating against those same three strains that have been genetically modified to minimize symptoms of illness.

LAIV is not recommended for individuals under age 2 or over age 50, but might be comparatively more effective among children over age 2.

A military study on military personnel showed that flu shots yielded less illness than nasal spray. Based on one of the largest head-to-head studies comparing LAIV and TIV (which was conducted by the U.S. Armed Forces Surveillance Center on military personnel who were stationed in the United States during three flu seasons from 2004 through 2007), investigators concluded that: "It may be prudent to use TIV in patients who were vaccinated at least once in the past 2 years [...] but LAIV against pandemic strains may be more protective than inactivated vaccines, because the population will probably lack preexisting immunity."

High-dose vaccine

A high-dose vaccine (Fluzone High-Dose) 4x the strength of standard flu vaccine was approved by the FDA in late 2009. This vaccine is intended for people 65 and over, who typically have weakened immune response due to normal aging. The vaccine produces a greater immune response than standard vaccine, but it is not yet known whether it provides greater protection against flu. Study results are expected in 2012. CDC recommends the high-dose vaccine for people 65 and over but expresses no preference between it and standard vaccine.

Vaccination recommendations

Various public health organizations, including the World Health Organization, have recommended that yearly influenza vaccination be routinely offered to patients at risk of complications of influenza and those individuals who live with or care for high-risk individuals, including:

the elderly (UK recommendation is those aged 65 or above)
patients with chronic lung diseases (asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...

, COPD, etc.)
patients with chronic heart diseases (congenital heart disease, chronic heart failure, ischaemic heart disease
Ischaemic heart disease
Ischaemic or ischemic heart disease , or myocardial ischaemia, is a disease characterized by ischaemia of the heart muscle, usually due to coronary artery disease...

)
patients with chronic liver diseases (including cirrhosis
Cirrhosis
Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...

)
patients with chronic renal diseases (such as the nephrotic syndrome
Nephrotic syndrome
Nephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....

)
patients who are immunosuppressed (those with HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...

or who are receiving drugs to suppress the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

such as chemotherapy and long-term steroids) and their household contacts
people who live together in large numbers in an environment where influenza can spread rapidly, such as prisons, nursing homes, schools, and dormitories
healthcare workers (both to prevent sickness and to prevent spread to patients)
pregnant women. However, a 2009 review concluded that there was insufficient evidence to recommend routine use of trivalent influenza vaccine during the first trimester of pregnancy.
children from ages six months to two years

Both types of flu vaccines are contraindicated for those with severe allergies

Allergy

An Allergy is a hypersensitivity disorder of the immune system. Allergic reactions occur when a person's immune system reacts to normally harmless substances in the environment. A substance that causes a reaction is called an allergen. These reactions are acquired, predictable, and rapid...

to egg proteins and people with a history of Guillain-Barré syndrome

Guillain-Barré syndrome

.
Public Health Law

Public health law

Law is an important public health tool that plays a critical role in reducing illness and premature death. Public health law examines the authority of the government at various jurisdictional levels to improve the health of the general population within societal limits and norms.Public health law...

Research, an independent organization, published in 2009 several evidence briefs summarizing the research assessing the effect of specific laws and policy on public health.

There is sufficient evidence supporting the effectiveness of requiring vaccinations as a condition for attending child care facilities and schools.

There is insufficient evidence to assess the effectiveness of requiring vaccinations as a condition for specified jobs as a means of reducing incidence of specific diseases among particularly vulnerable populations.

There is strong evidence supporting the effectiveness of standing orders which allow healthcare workers without prescription authority to administer vaccines under defined circumstances as a public health intervention aimed at increasing vaccination rates.

Side effects

Side effects of the flu vaccine injection include:

mild soreness, redness, and swelling where the shot was given
fever
aches

These problems usually begin soon after the injection, and last 1–2 days.

Side effects of the activated/live/LAIV flu nasal spray vaccine:

Some children and adolescents 2–17 years of age have reported:

runny nose, nasal congestion or cough
fever
headache and muscle aches
wheezing
abdominal pain or occasional vomiting or diarrhea

Some adults 18–49 years of age have reported:

runny nose or nasal congestion
sore throat
cough, chills, tiredness/weakness
headache

More severe, but very rare side effects include:

life-threatening allergic reaction

Some injection-based flu vaccines intended for adults in the United States contain thiomersal

Thiomersal

Thiomersal , and commonly known in the US as thimerosal, is an organomercury compound. This compound is a well established antiseptic and antifungal agent....

(also known as thimerosal). Despite some controversy

Thiomersal controversy

The thiomersal controversy describes claims that vaccines containing the mercury-based preservative thiomersal contribute to the development of autism and other brain development disorders...

in the media, the World Health Organization

World Health Organization

The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

has concluded that there is no evidence of toxicity from thiomersal in vaccines and no reason on grounds of safety to change to more-expensive single-dose administration.

Although Guillain-Barré syndrome had been feared as a complication of vaccination, the CDC states that most studies on modern influenza vaccines have seen no link with Guillain-Barré.

A review has concluded that the 2009 H1N1 ("swine flu") vaccine has a safety profile similar to that of seasonal vaccine. Although one review gives an incidence of about one case per million vaccinations, a large study in China, reported in the NEJM covering close to 100 million doses of vaccine against the 2009 H1N1 "swine" flu found only eleven cases of Guillain-Barre syndrome

Guillain-Barré syndrome

, (0.1%) total incidence in persons vaccinated, actually lower than the normal rate of the disease in China, and no other notable side effects; "The risk-benefit ratio, which is what vaccines and everything in medicine is about, is overwhelmingly in favor of vaccination." Getting infected by influenza itself increases both the risk of death (up to 1 in 10,000) and increases the risk of developing Guillain-Barré syndrome

Guillain-Barré syndrome

to a much higher level than the highest level of suspected vaccine involvement (approx. 10 times higher by recent estimates).

Flu vaccine manufacturing

Flu vaccine is usually grown in fertilized chicken

Chicken

The chicken is a domesticated fowl, a subspecies of the Red Junglefowl. As one of the most common and widespread domestic animals, and with a population of more than 24 billion in 2003, there are more chickens in the world than any other species of bird...

eggs. In February preceding each fall's flu season (in the Northern hemisphere), three strains of flu are selected and chicken eggs inoculated.

As of November 2007, both the conventional injection and the nasal spray are manufactured using chicken eggs. The European Union has also approved Optaflu

Optaflu

Optaflu is a cell culture derived influenza vaccine manufactured by Novartis.-History:On April 27, 2007 Novartis received a positive opinion supporting European Union approval of Optaflu. It is the first influenza vaccine made in a mammalian cell line, rather than chicken eggs. The vaccine will be...

, a vaccine produced by Novartis

Novartis

Novartis International AG is a multinational pharmaceutical company based in Basel, Switzerland, ranking number three in sales among the world-wide industry...

using vats of animal cells. This technique is expected to be more scalable and avoid problems with eggs, such as allergic reactions and incompatibility with strains that affect avians like chickens. A DNA-based vaccination, which is hoped to be even faster to manufacture, is currently in clinical trials, but has not yet been proven safe and effective. Research continues into the idea of a "universal" influenza vaccine (but no vaccine candidates have been announced) which would not need to be tailored to work on particular strains, but would be effective against a broad variety of influenza viruses.

In a 2007 report, the current global capacity of approximately 826 million seasonal
influenza vaccine doses (inactivated and live) was double the current production of 413 million
doses. In an aggressive scenario of producing pandemic influenza vaccines by 2013, only 2.8 billion courses could be produced in a six-month time frame. If all high- and upper-middle-income countries sought vaccines for their entire populations in a pandemic, nearly 2 billion courses would be required. If China pursued this goal as well, more than 3 billion courses would be required to serve these populations. Vaccine research and development is ongoing to identify novel vaccine approaches that could produce much greater quantities of vaccine at a price that is affordable to the global population.

An effective method of vaccine generation that bypasses the need for eggs is the construction of "influenza virus-like particle (VLP)". VLP is a non-egg, non-mammalian cell culture-based vaccine, purified from the supernatants of Spodoptera frugiperda Sf9 insect cells following infection of baculovirus vectors encoding an expression cassette made up of only three influenza virus structural proteins, hemagglutinin (HA), neuraminidase (NA), and matrix (M1) VLPs elicit antibodies that recognize a broader panel of antigenically distinct viral isolates compared to other vaccines in the hemagglutination-inhibition (HAI) assay.

H5N1

Vaccines have been formulated against several of the avian H5N1

H5N1

Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...

influenza varieties. Vaccination of poultry against the ongoing H5N1 epizootic

Epizootic

In epizoology, an epizootic is a disease that appears as new cases in a given animal population, during a given period, at a rate that substantially exceeds what is "expected" based on recent experience . Epidemic is the analogous term applied to human populations...

is widespread in certain countries. Some vaccines also exist for use in humans, and others are in testing, but none have been made available to civilian populations, nor produced in quantities sufficient to protect more than a tiny fraction of the Earth's population in the event of an H5N1 pandemic

Pandemic

A pandemic is an epidemic of infectious disease that is spreading through human populations across a large region; for instance multiple continents, or even worldwide. A widespread endemic disease that is stable in terms of how many people are getting sick from it is not a pandemic...

.

Three H5N1 vaccines for humans have been licensed as of June 2008:

Sanofi Pasteur
Sanofi pasteur
Sanofi Pasteur is the vaccines division of sanofi-aventis Group. It is the largest company in the world devoted entirely to vaccines.- History :...

's vaccine approved by the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

in April 2007,
GlaxoSmithKline
GlaxoSmithKline
GlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom...

's vaccine Pandemrix
Pandemrix
Pandemrix is an influenza vaccine for influenza pandemics, such as the H1N1 2009 flu pandemic colloquially called the swine flu. The vaccine was developed by GlaxoSmithKline and patented in September 2006....

approved by the European Union
European Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...

in May 2008, and
CSL Limited
CSL Limited
CSL Limited is a global specialty biopharmaceutical company that researches, develops, manufactures and markets products to treat and prevent serious human medical conditions...

's vaccine approved by Australia
Australia
Australia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans. It is the world's sixth-largest country by total area...

in June 2008.

All are produced in eggs and would require many months to be altered to a pandemic version.

H5N1 continually mutates, meaning vaccines based on current samples of avian H5N1 cannot be depended upon to work in the case of a future pandemic of H5N1. While there can be some cross-protection against related flu strains, the best protection would be from a vaccine specifically produced for any future pandemic flu virus strain. Dr. Daniel Lucey, co-director of the Biohazardous Threats and Emerging Diseases graduate program at Georgetown University, has made this point, "There is no H5N1

H5N1

Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...

pandemic

Pandemic

so there can be no pandemic vaccine

Vaccine

." However, "pre-pandemic vaccines" have been created; are being refined and tested; and do have some promise both in furthering research and preparedness for the next pandemic. Vaccine manufacturing companies are being encouraged to increase capacity so that if a pandemic vaccine is needed, facilities will be available for rapid production of large amounts of a vaccine specific to a new pandemic strain.

Problems with H5N1

H5N1

Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...

vaccine production include:

lack of overall production capacity
lack of surge production capacity (it is impractical to develop a system that depends on hundreds of millions of 11-day old specialized eggs on a standby basis)
the pandemic H5N1 might be lethal to chickens

Cell culture

Cell culture is the complex process by which cells are grown under controlled conditions. In practice, the term "cell culture" has come to refer to the culturing of cells derived from singlecellular eukaryotes, especially animal cells. However, there are also cultures of plants, fungi and microbes,...

(cell-based) manufacturing technology can be applied to influenza vaccines as they are with most viral vaccines and thereby solve the problems associated with creating flu vaccines using chicken eggs as is currently done.:

Currently, influenza vaccine for the annual, seasonal influenza program comes from four manufacturers. However, only a single manufacturer produces the annual vaccine

Vaccine

entirely within the U.S. Thus, if a pandemic occurred and existing U.S.-based influenza vaccine manufacturing capacity was completely diverted to producing a pandemic vaccine, supply would be severely limited. Moreover, because the annual influenza manufacturing process takes place during most of the year, the time and capacity to produce vaccine against potential pandemic viruses for a stockpile, while continuing annual influenza vaccine production, is limited. Since supply will be limited, it is critical for HHS to be able to direct vaccine distribution in accordance with predefined groups (see Appendix D); HHS will ensure the building of capacity and will engage states in a discussion about the purchase and distribution of pandemic influenza vaccine.

Vaccine production capacity: The protective immune response generated by current influenza vaccines is largely based on viral hemagglutinin

Hemagglutinin

Influenza hemagglutinin or haemagglutinin is a type of hemagglutinin found on the surface of the influenza viruses. It is an antigenic glycoprotein. It is responsible for binding the virus to the cell that is being infected...

(HA) and neuraminidase

Neuraminidase

Neuraminidase enzymes are glycoside hydrolase enzymes that cleave the glycosidic linkages of neuraminic acids. Neuraminidase enzymes are a large family, found in a range of organisms. The most commonly known neuraminidase is the viral neuraminidase, a drug target for the prevention of the spread...

(NA) antigen

Antigen

An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...

s in the vaccine. As a consequence, the basis of influenza vaccine manufacturing is growing massive quantities of virus in order to have sufficient amounts of these protein antigens to stimulate immune responses. Influenza vaccines used in the United States and around world are manufactured by growing virus in fertilized hens' egg

Egg (biology)

An egg is an organic vessel in which an embryo first begins to develop. In most birds, reptiles, insects, molluscs, fish, and monotremes, an egg is the zygote, resulting from fertilization of the ovum, which is expelled from the body and permitted to develop outside the body until the developing...

s, a commercial process that has been in place for decades. To achieve current vaccine production targets millions of 11-day old fertilized eggs must be available every day of production.

In the near term, further expansion of these systems will provide additional capacity for the U.S.-based production of both seasonal and pandemic vaccines, however, the surge capacity that will be needed for a pandemic response cannot be met by egg-based vaccine production alone, as it is impractical to develop a system that depends on hundreds of millions of 11-day old specialized eggs on a standby basis. In addition, because a pandemic could result from an avian influenza strain that is lethal to chicken

Chicken

s, it is impossible to ensure that eggs will be available to produce vaccine when needed.

In contrast, cell culture

Cell culture

manufacturing technology

Technology

Technology is the making, usage, and knowledge of tools, machines, techniques, crafts, systems or methods of organization in order to solve a problem or perform a specific function. It can also refer to the collection of such tools, machinery, and procedures. The word technology comes ;...

can be applied to influenza vaccines as they are with most viral vaccines (e.g., polio vaccine, measles

Measles

Measles, also known as rubeola or morbilli, is an infection of the respiratory system caused by a virus, specifically a paramyxovirus of the genus Morbillivirus. Morbilliviruses, like other paramyxoviruses, are enveloped, single-stranded, negative-sense RNA viruses...

-mumps

Mumps

Mumps is a viral disease of the human species, caused by the mumps virus. Before the development of vaccination and the introduction of a vaccine, it was a common childhood disease worldwide...

-rubella

Rubella

Rubella, commonly known as German measles, is a disease caused by the rubella virus. The name "rubella" is derived from the Latin, meaning little red. Rubella is also known as German measles because the disease was first described by German physicians in the mid-eighteenth century. This disease is...

vaccine, chickenpox

Chickenpox

Chickenpox or chicken pox is a highly contagious illness caused by primary infection with varicella zoster virus . It usually starts with vesicular skin rash mainly on the body and head rather than at the periphery and becomes itchy, raw pockmarks, which mostly heal without scarring...

vaccine). In this system, viruses are grown in closed systems such as bioreactor

Bioreactor

A bioreactor may refer to any manufactured or engineered device or system that supports a biologically active environment. In one case, a bioreactor is a vessel in which a chemical process is carried out which involves organisms or biochemically active substances derived from such organisms. This...

s containing large numbers of cells in growth media rather than eggs. The surge capacity afforded by cell-based technology is insensitive to seasons and can be adjusted to vaccine demand, as capacity can be increased or decreased by the number of bioreactors or the volume used within a bioreactor. In addition to supporting basic research on cell-based influenza vaccine development, HHS is currently supporting a number of vaccine manufacturers in the advanced development of cell-based influenza vaccines with the goal of developing U.S.-licensed cell-based influenza vaccines produced in the United States. The US government has purchased from Sanofi Pasteur

Sanofi pasteur

Sanofi Pasteur is the vaccines division of sanofi-aventis Group. It is the largest company in the world devoted entirely to vaccines.- History :...

and Chiron Corporation

Chiron Corporation

Chiron Corporation was a multinational biotechnology firm based in Emeryville, California that was acquired by Novartis International AG on April 20, 2006. It had offices and facilities in eighteen countries on five continents. Chiron's business and research was in three main areas:...

several million doses of vaccine

Vaccine

meant to be used in case of an influenza pandemic

Influenza pandemic

of H5N1

H5N1

Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...

avian influenza and is conducting clinical trials with these vaccines. Researchers at the University of Pittsburgh have had success with a genetically engineered vaccine that took only a month to make and completely protected chickens from the highly pathogenic H5N1

H5N1

Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...

virus.

According to the United States

United States

The United States of America is a federal constitutional republic comprising fifty states and a federal district...

Department of Health & Human Services:

In addition to supporting basic research on cell-based influenza vaccine development, HHS is currently supporting a number of vaccine

Vaccine

manufacturers in the advanced development of cell-based influenza vaccines with the goal of developing U.S.-licensed cell-based influenza vaccines produced in the United States. Dose-sparing technologies. Current U.S.-licensed vaccines stimulate an immune response based on the quantity of HA (hemagglutinin

Hemagglutinin

) antigen

Antigen

included in the dose. Methods to stimulate a strong immune response using less HA antigen are being studied in H5N1

H5N1

Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...

and H9N2 vaccine trials. These include changing the mode of delivery from intramuscular to intradermal and the addition of immune-enhancing adjuvant

Immunologic adjuvant

In immunology, an adjuvant is an agent that may stimulate the immune system and increase the response to a vaccine, without having any specific antigenic effect in itself. The word “adjuvant” comes from the Latin word adiuvare, meaning to help or aid...

to the vaccine formulation. Additionally, HHS is soliciting contract proposals from manufacturers of vaccine

Vaccine

s, adjuvant

Immunologic adjuvant

s, and medical devices for the development and licensure of influenza vaccines that will provide dose-sparing alternative strategies.

Chiron Corporation

is now recertified and under contract with the National Institutes of Health

National Institutes of Health

The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...

to produce 8,000–10,000 investigational doses of Avian Flu (H5N1) vaccine

H5N1

Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...

. MedImmune

MedImmune

MedImmune, LLC, headquartered in Gaithersburg, Maryland, became a wholly owned subsidiary of AstraZeneca in 2007. Since being acquired, MedImmune has remained a Maryland-based biotechnology development enterprise...

and Aventis Pasteur are under similar contracts. The United States

United States

The United States of America is a federal constitutional republic comprising fifty states and a federal district...

government hopes to obtain enough vaccine

Vaccine

in 2006 to treat 4 million people. However, it is unclear whether this vaccine would be effective against a hypothetical mutated strain that would be easily transmitted through human populations, and the shelflife of stockpiled doses has yet to be determined.

The New England Journal of Medicine
New England Journal of Medicine
The New England Journal of Medicine is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It describes itself as the oldest continuously published medical journal in the world.-History:...

reported on March 30, 2006 on one of dozens of vaccine studies currently being conducted. The Treanor et al. study was on vaccine produced from the human isolate (A/Vietnam/1203/2004 H5N1

H5N1

Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...

) of a virulent clade 1 influenza A (H5N1) virus with the use of a plasmid rescue system, with only the hemagglutinin and neuraminidase genes expressed and administered without adjuvant. "The rest of the genes were derived from an avirulent egg-adapted influenza A/PR/8/34 strain. The hemagglutinin gene was further modified to replace six basic amino acids associated with high pathogenicity in birds at the cleavage site between hemagglutinin 1 and hemagglutinin 2. Immunogenicity was assessed by microneutralization and hemagglutination-inhibition assays with the use of the vaccine virus, although a subgroup of samples were tested with the use of the wild-type influenza A/Vietnam/1203/2004 (H5N1) virus." The results of this study combined with others scheduled to be completed by spring 2007 is hoped will provide a highly immunogenic vaccine that is cross-protective against heterologous influenza strains.

On August 18, 2006. the World Health Organization

World Health Organization

changed the H5N1

H5N1

Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...

strains recommended for candidate vaccines for the first time since 2004. "The WHO's new prototype strains, prepared by reverse genetics, include three new H5N1 subclades. The hemagglutinin

Hemagglutinin

sequences of most of the H5N1 avian influenza viruses circulating in the past few years fall into two genetic groups, or clades. Clade 1 includes human and bird isolates from Vietnam

Vietnam

Vietnam – sometimes spelled Viet Nam , officially the Socialist Republic of Vietnam – is the easternmost country on the Indochina Peninsula in Southeast Asia. It is bordered by China to the north, Laos to the northwest, Cambodia to the southwest, and the South China Sea –...

, Thailand

Thailand

Thailand , officially the Kingdom of Thailand , formerly known as Siam , is a country located at the centre of the Indochina peninsula and Southeast Asia. It is bordered to the north by Burma and Laos, to the east by Laos and Cambodia, to the south by the Gulf of Thailand and Malaysia, and to the...

, and Cambodia

Cambodia

Cambodia , officially known as the Kingdom of Cambodia, is a country located in the southern portion of the Indochina Peninsula in Southeast Asia...

and bird isolates from Laos

Laos

Laos Lao: ສາທາລະນະລັດ ປະຊາທິປະໄຕ ປະຊາຊົນລາວ Sathalanalat Paxathipatai Paxaxon Lao, officially the Lao People's Democratic Republic, is a landlocked country in Southeast Asia, bordered by Burma and China to the northwest, Vietnam to the east, Cambodia to the south and Thailand to the west...

and Malaysia. Clade 2 viruses were first identified in bird isolates from China

China

Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...

, Indonesia

Indonesia

Indonesia , officially the Republic of Indonesia , is a country in Southeast Asia and Oceania. Indonesia is an archipelago comprising approximately 13,000 islands. It has 33 provinces with over 238 million people, and is the world's fourth most populous country. Indonesia is a republic, with an...

, Japan

Japan

Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...

, and South Korea

South Korea

The Republic of Korea , , is a sovereign state in East Asia, located on the southern portion of the Korean Peninsula. It is neighbored by the People's Republic of China to the west, Japan to the east, North Korea to the north, and the East China Sea and Republic of China to the south...

before spreading westward to the Middle East

Middle East

The Middle East is a region that encompasses Western Asia and Northern Africa. It is often used as a synonym for Near East, in opposition to Far East...

, Europe

Europe

Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...

, and Africa

Africa

Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...

. The clade 2 viruses have been primarily responsible for human H5N1 infections that have occurred during late 2005 and 2006, according to WHO. Genetic analysis has identified six subclades of clade 2, three of which have a distinct geographic distribution and have been implicated in human infections:

Subclade 1, Indonesia
Subclade 2, Middle East, Europe, and Africa
Subclade 3, China

On the basis of the three subclades, the WHO is offering companies and other groups that are interested in pandemic vaccine development these three new prototype strains:

An A/Indonesia/2/2005-like virus
An A/Bar headed goose/Quinghai/1A/2005-like virus
An A/Anhui/1/2005-like virus

[...] Until now, researchers have been working on prepandemic vaccines for H5N1 viruses in clade 1. In March, the first clinical trial of a U.S. vaccine for H5N1 showed modest results. In May, French researchers showed somewhat better results in a clinical trial of an H5N1 vaccine that included an adjuvant. Vaccine experts aren't sure if a vaccine effective against known H5N1 viral strains would be effective against future strains. Although the new viruses will now be available for vaccine research, WHO said clinical trials using the clade 1 viruses should continue as an essential step in pandemic preparedness, because the trials yield useful information on priming, cross-reactivity, and cross-protection by vaccine viruses from different clades and subclades."

As of November 2006, the United States Department of Health and Human Services still had enough H5N1 pre-pandemic vaccine to treat about 3 million people (5.9 million full-potency doses) in spite of 0.2 million doses used for research and 1.4 million doses that have begun to lose potency (from the original 7.5 million full-potency doses purchased from Sanofi Pasteur

Sanofi pasteur

Sanofi Pasteur is the vaccines division of sanofi-aventis Group. It is the largest company in the world devoted entirely to vaccines.- History :...

and Chiron Corp.). The expected shelf life of seasonal flu vaccine is about a year so the fact that most of the H5N1 pre-pandemic stockpile is still good after about 2 years is considered encouraging.

Annual reformulation of flu vaccine

Each year, three strains are chosen for selection in that year's flu vaccination by the WHO Global Influenza Surveillance Network

National Influenza Centers

National Influenza Centers are institutions which are formally recognized as such by the World Health Organization ."The WHO Global Influenza Surveillance Network was established in 1952...

. The chosen strains are the H1N1, H3N2, and Type-B strains thought most likely to cause significant human suffering in the coming season. Due to the high mutation rate

Mutation rate

In genetics, the mutation rate is the chance of a mutation occurring in an organism or gene in each generation...

of the virus a particular vaccine

Vaccine

formulation is effective for at most about a year. The World Health Organization

World Health Organization

coordinates the contents of the vaccine each year to contain the most likely strains of the virus to attack the next year.

"The WHO Global Influenza Surveillance Network

National Influenza Centers

National Influenza Centers are institutions which are formally recognized as such by the World Health Organization ."The WHO Global Influenza Surveillance Network was established in 1952...

was established in 1952. The network comprises 4 WHO Collaborating Centres (WHO CCs) and 112 institutions in 83 countries, which are recognized by WHO as WHO National Influenza Centres (NICs). These NICs collect specimens in their country, perform primary virus isolation and preliminary antigenic characterization. They ship newly isolated strains to WHO CCs for high level antigenic and genetic analysis, the result of which forms the basis for WHO

Who

Who may refer to:* Who , an English-language pronoun* who , a Unix command* Who?, one of the Five Ws in journalism- Art and entertainment :* Who? , a 1958 novel by Algis Budrys...

recommendations on the composition of influenza vaccine for the Northern and Southern Hemisphere each year."

The Global Influenza Surveillance Network

National Influenza Centers

National Influenza Centers are institutions which are formally recognized as such by the World Health Organization ."The WHO Global Influenza Surveillance Network was established in 1952...

's selection of viruses for the vaccine manufacturing process is based on its best estimate of which strains will be predominant the next year, amounting in the end to well-informed but fallible guesswork.

Formal WHO recommendations first issued in 1973; beginning 1999 there have been two recommendations per year, one for the northern hemisphere (N) and the other for the southern hemisphere (S).

History of past WHO seasonal influenza vaccine composition recommendations:

2002–2003 Northern Hemisphere winter season

The vaccine

Vaccine

s produced for the 2002–2003 season use:

an A/New Caledonia/20/1999-like(H1N1
H1N1
'Influenza A virus is a subtype of influenza A virus and was the most common cause of human influenza in 2009. Some strains of H1N1 are endemic in humans and cause a small fraction of all influenza-like illness and a small fraction of all seasonal influenza. H1N1 strains caused a few percent of...

);
an A/Moscow/10/1999-like(H3N2
H3N2
Influenza A virus subtype H3N2 is a subtype of viruses that cause influenza . H3N2 Viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains...

);
a B/Hong Kong/330/2001-like viruses.

2003 Southern Hemisphere winter season

The composition of influenza virus vaccines for use in the 2003 Southern Hemisphere influenza season recommended by the World Health Organization was:

an A/New Caledonia/20/99(H1N1)-like virus
an A/Moscow/10/99(H3N2)-like virus (The widely used vaccine strain is A/Panama/2007/99)
a B/Hong Kong/330/2001-like virus (Some vaccine strains used were B/Shandong/7/97, B/Hong Kong/330/2001, B/Hong Kong/1434/2002)

2003–2004 Northern Hemisphere winter season

The production of flu vaccine

Vaccine

requires a lead time of about six months before the season. It is possible that by flu season a strain becomes common for which the vaccine does not provide protection. In the 2003–2004 season the vaccine

Vaccine

was produced to protect against A/Panama, A/New Caledonia, and B/Hong Kong. A new strain, A/Fujian, was discovered after production of the vaccine started and vaccination gave only partial protection against this strain.

Nature magazine reported that the Influenza Genome Sequencing Project

Influenza Genome Sequencing Project

The Influenza Genome Sequencing Project is an American-based genome project aimed at improving the availability of genomic sequence data from influenza viruses and related information....

, using phylogenetic analysis of 156 H3N2

H3N2

Influenza A virus subtype H3N2 is a subtype of viruses that cause influenza . H3N2 Viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains...

genomes, "explains the appearance, during the 2003–2004 season, of the 'Fujian/411/2002'-like strain, for which the existing vaccine had limited effectiveness" as due to an epidemiologically significant reassortment

Reassortment

Reassortment is the mixing of the genetic material of a species into new combinations in different individuals. Several different processes contribute to reassortment, including assortment of chromosomes, and chromosomal crossover. It is particularly used when two similar viruses that are infecting...

. "Through a reassortment

Reassortment

event, a minor clade provided the haemagglutinin gene that later became part of the dominant strain after the 2002–2003 season. Two of our samples, A/New York/269/2003 (H3N2

H3N2

Influenza A virus subtype H3N2 is a subtype of viruses that cause influenza . H3N2 Viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains...

) and A/New York/32/2003 (H3N2

H3N2

Influenza A virus subtype H3N2 is a subtype of viruses that cause influenza . H3N2 Viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains...

), show that this minor clade continued to circulate in the 2003–2004 season, when most other isolates were reassortants."

According to the CDC

Centers for Disease Control and Prevention

During the 2003–2004 influenza season

Flu season

, influenza A

Influenzavirus A

Influenza A virus causes influenza in birds and some mammals and is the only species of Influenzavirus A. Influenzavirus A is a genus of the Orthomyxoviridae family of viruses. Strains of all subtypes of influenza A virus have been isolated from wild birds, although disease is uncommon...

(H1), A (H3N2

H3N2

Influenza A virus subtype H3N2 is a subtype of viruses that cause influenza . H3N2 Viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains...

), and B

Influenzavirus B

Influenzavirus B is a genus in the virus family Orthomyxoviridae. The only species in this genus is called "Influenza B virus".Influenza B viruses are only known to infect humans and seals, giving them influenza...

viruses co-circulated worldwide, and influenza A (H3N2) virus

Virus

A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...

es predominated. Several Asian countries reported widespread outbreaks of avian influenza A (H5N1

H5N1

Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...

) among poultry. In Vietnam

Vietnam

and Thailand

Thailand

, these outbreaks were associated with severe illnesses and deaths among humans. In the United States

United States

The United States of America is a federal constitutional republic comprising fifty states and a federal district...

, the 2003–2004 influenza season began earlier than most seasons, peaked in December, was moderately severe in terms of its impact on mortality, and was associated predominantly with influenza A (H3N2) viruses.

During September 28, 2003 – May 22, 2004, WHO

Who

Who may refer to:* Who , an English-language pronoun* who , a Unix command* Who?, one of the Five Ws in journalism- Art and entertainment :* Who? , a 1958 novel by Algis Budrys...

and NREVSS collaborating laboratories in the United States tested 130,577 respiratory specimens for influenza viruses; 24,649 (18.9%) were positive. Of these, 24,393 (99.0%) were influenza A viruses, and 249 (1.0%) were influenza B viruses. Among the influenza A viruses, 7,191 (29.5%) were subtyped; 7,189 (99.9%) were influenza A (H3N2) viruses, and two (0.1%) were influenza A (H1) viruses. The proportion of specimens testing positive for influenza first increased to >10% during the week ending October 25, 2003 (week 43), peaked at 35.2% during the week ending November 29 (week 48), and declined to <10% during the week ending January 17, 2004 (week 2). The peak percentage of specimens testing positive for influenza during the previous four seasons had ranged from 23% to 31% and peaked during late December to late February.

As of June 15, 2004, CDC had antigenically characterized 1,024 influenza viruses collected by U.S. laboratories since October 1, 2003: 949 influenza A (H3N2

H3N2

Influenza A virus subtype H3N2 is a subtype of viruses that cause influenza . H3N2 Viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains...

) viruses, three influenza A (H1) viruses, one influenza A (H7N2

H7N2

H7N2 is a subtype of the species Influenza A virus .A CDC study following outbreaks of H7N2 in commercial poultry farms in western Virginia in 2002 concluded:...

) virus, and 71 influenza B viruses. Of the 949 influenza A (H3N2) isolates characterized, 106 (11.2%) were similar antigenically to the vaccine strain A/Panama/2007/99 (H3N2), and 843 (88.8%) were similar to the drift variant, A/Fujian/411/2002 (H3N2). Of the three A (H1) isolates that were characterized, two were H1N1 viruses, and one was an H1N2

H1N2

H1N2 is a subtype of the species Influenza A virus . It is currently pandemic in both human and pig populations.H1N1, H1N2, and H3N2 are the only known Influenza A virus subtypes currently circulating among humans....

virus. The hemagglutinin proteins of the influenza A (H1) viruses were similar antigenically to the hemagglutinin of the vaccine strain A/New Caledonia/20/99. Of the 71 influenza B isolates that were characterized, 66 (93%) belonged to the B/Yamagata/16/88 lineage and were similar antigenically to B/Sichuan/379/99, and five (7%) belonged to the B/Victoria/2/87 lineage and were similar antigenically to the corresponding vaccine strain B/Hong Kong/330/2001.

H9N2
In December 2003, one confirmed case of avian influenza A (H9N2

H9N2

H9N2 is a subtype of the species Influenza A virus ."H9N2 influenza viruses of domestic ducks have become established in the domestic poultry of Asia. Phylogenetic and antigenic analyses of the H9N2 viruses isolated from Hong Kong markets suggest three distinct sublineages...

) virus infection was reported in a child aged five years in Hong Kong. The child had fever, cough, and nasal discharge in late November, was hospitalized for two days, and fully recovered. The source of this child's H9N2 infection is unknown.

H5N1
During January–March 2004, a total of 34 confirmed human cases of avian influenza A (H5N1

H5N1

Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...

) virus infection were reported in Vietnam and Thailand. The cases were associated with severe respiratory illness requiring hospitalization and a case-fatality proportion of 68% (Vietnam: 22 cases, 15 deaths; Thailand: 12 cases, eight deaths). A substantial proportion of the cases were among children and young adults (i.e., persons aged 5–24 years). These cases were associated with widespread outbreaks of highly pathogenic H5N1 influenza among domestic poultry.

H7N3
During March 2004, health authorities in Canada reported two confirmed cases of avian influenza A (H7N3

H7N3

H7N3 is a subtype of the species Influenza A virus .In North America, the presence of H7N3 was confirmed at several poultry farms in British Columbia in February 2004. As of April 2004, 18 farms had been quarantined to halt the spread of the virus. Two cases of humans infected with it have been...

) virus infection in poultry workers who were involved in culling of poultry during outbreaks of highly pathogenic H7N3 on farms in the Fraser River Valley, British Columbia. One patient had unilateral conjunctivitis

Conjunctivitis

Conjunctivitis refers to inflammation of the conjunctiva...

and nasal discharge, and the other had unilateral conjunctivitis and headache. Both illnesses resolved without hospitalization.

H7N2
During the 2003–2004 influenza season, a case of avian influenza A (H7N2

H7N2

H7N2 is a subtype of the species Influenza A virus .A CDC study following outbreaks of H7N2 in commercial poultry farms in western Virginia in 2002 concluded:...

) virus infection was detected in an adult male from New York, who was hospitalized for upper and lower respiratory tract illness in November 2003. Influenza A (H7N2) virus was isolated from a respiratory specimen from the patient, whose acute symptoms resolved. The source of this person's infection is unknown.

2004 Southern Hemisphere winter season

The composition of influenza virus vaccines for use in the 2004 Southern Hemisphere influenza season recommended by the World Health Organization was:

an A/New Caledonia/20/99(H1N1)-like virus
an A/Fujian/411/2002(H3N2)-like virus (A/Kumamoto/102/2002 and A/Wyoming/3/2003 were egg-grown A/Fujian/411/2002-like viruses)
a B/Hong Kong/330/2001-like virus (B/Shandong/7/97, B/Hong Kong/330/2001 and B/Hong Kong/1434/2002 were among those used at the time. B/Brisbane/32/2002 was also available.)

2004–2005 Northern Hemisphere winter season

According to the CDC

Centers for Disease Control and Prevention

On the basis of antigenic analyses of recently isolated influenza viruses, epidemiologic data, and postvaccination serologic studies in humans, the Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee (VRBPAC) recommended that the 2004–05 trivalent influenza vaccine for the United States contain A/New Caledonia/20/99-like (H1N1), A/Fujian/411/2002-like (H3N2)

Fujian flu

Fujian flu refers to flu caused by either a Fujian human flu strain of the H3N2 subtype of the Influenza A virus or a Fujian bird flu strain of the H5N1 subtype of the Influenza A virus...

, and B/Shanghai/361/2002-like viruses. Because of the growth properties of the A/Wyoming/3/2003 and B/Jiangsu/10/2003 viruses, U.S. vaccine manufacturers are using these antigenically equivalent strains in the vaccine as the H3N2 and B components, respectively. The A/New Caledonia/20/99 virus will be retained as the H1N1 component of the vaccine.

2005 Southern Hemisphere winter season

The composition of influenza virus vaccines for use in the 2005 Southern Hemisphere influenza season recommended by the World Health Organization was:

an A/New Caledonia/20/99(H1N1)-like virus;
an A/Wellington/1/2004(H3N2)-like virus;
a B/Shanghai/361/2002-like virus (B/Shanghai/361/2002, B/Jilin/20/2003 and B/Jiangsu/10/2003 were used at the time)

2005–2006 Northern Hemisphere winter season

The vaccine

Vaccine

s produced for the 2005–2006 season use:

an A/New Caledonia/20/1999-like(H1N1
H1N1
'Influenza A virus is a subtype of influenza A virus and was the most common cause of human influenza in 2009. Some strains of H1N1 are endemic in humans and cause a small fraction of all influenza-like illness and a small fraction of all seasonal influenza. H1N1 strains caused a few percent of...

);
an A/California/7/2004-like(H3N2
H3N2
Influenza A virus subtype H3N2 is a subtype of viruses that cause influenza . H3N2 Viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains...

) (or the antigenically equivalent strain A/New York/55/2004);
a B/Jiangsu/10/2003-like viruses.

In people in the United States, overall flu and pneumonia

Pneumonia

Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...

deaths were below those of a typical flu season

Flu season

with 84% Influenzavirus A

Influenzavirus A

and the rest Influenzavirus B

Influenzavirus B

. Of the patients who had Type A viruses, 80% had viruses identical or similar to the A bugs in the vaccine. 70% of the people testing positive for a B virus had Type B Victoria, a version not found in the vaccine.

"During the 2005–06 season, influenza A (H3N2) viruses predominated overall, but late in the season influenza B viruses were more frequently isolated than influenza A viruses. Influenza A (H1N1) viruses circulated at low levels throughout the season. Nationally, activity was low from October through early January, increased during February, and peaked in early March. Peak activity was less intense, but activity remained elevated for a longer period of time this season compared to the previous three seasons. The longer period of elevated activity may be due in part to regional differences in the timing of peak activity and intensity of influenza B activity later in the season."

2006 Southern Hemisphere winter season

The composition of influenza virus vaccines for use in the 2006 Southern Hemisphere influenza season recommended by the World Health Organization was:

an A/New Caledonia/20/99(H1N1)-like virus;
an A/California/7/2004(H3N2)-like virus (A/New York/55/2004 was used at the time);
a B/Malaysia/2506/2004-like virus

2006–2007 Northern Hemisphere winter season

The 2006–2007 influenza vaccine composition recommended by the World Health Organization on February 15, 2006 and the U.S. FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) on February 17, 2006 use:

an A/New Caledonia/20/99 (H1N1)-like virus;
an A/Wisconsin/67/2005 (H3N2)-like virus (A/Wisconsin/67/2005 and A/Hiroshima/52/2005 strains);
a B/Malaysia/2506/2004-like virus from B/Malaysia/2506/2004 and B/Ohio/1/2005 strains which are of B/Victoria/2/87 lineage.

2007 Southern Hemisphere winter season

The composition of influenza virus vaccines for use in the 2007 Southern Hemisphere influenza season recommended by the World Health Organization on September 20, 2006 was:

an A/New Caledonia/20/99(H1N1)-like virus,
an A/Wisconsin/67/2005(H3N2)-like virus (A/Wisconsin/67/2005 and A/Hiroshima/52/2005 were used at the time),
a B/Malaysia/2506/2004-like virus

2007–2008 Northern Hemisphere winter season

The composition of influenza virus vaccines for use in the 2007–2008 Northern Hemisphere influenza season recommended by the World Health Organization on February 14, 2007 was:

an A/Solomon Islands/3/2006 (H1N1)-like virus;
an A/Wisconsin/67/2005 (H3N2)-like virus (A/Wisconsin/67/2005 (H3N2) and A/Hiroshima/52/2005 were used at the time);
a B/Malaysia/2506/2004-like virus

In the US, the CDC reported in Feb 2008 that the H1N1 component was a good match (96%) to the infections occurring. But 87% of the H3N2 are A/Brisbane/10/2007-like viruses, which are a recent antigenic variant of the vaccine strain, A/Wisconsin. And 93% of the B viruses are in a B/Yamagata lineage that is relatively distinct from the vaccine strain B/Victoria lineage. Only one of the three components was a good match; A/Wisconsin is moderately protective against the drifted A/Brisbane strain. 4.5% of those viruses tested are resistant to Oseltamivir

Oseltamivir

Oseltamivir INN , an antiviral drug, slows the spread of influenza virus between cells in the body by stopping the virus from chemically cutting ties with its host cell; median time to symptom alleviation is reduced by 0.5–1 day. The drug is sold under the trade name Tamiflu, and is taken orally...

, or Tamiflu—a significant increase over previous years.

This vaccine has been described as 40% effective compared to other years that have been 85–95% effective.

2008 Southern Hemisphere winter season

The composition of virus vaccines for use in the 2008 Southern Hemisphere influenza season recommended by the World Health Organization on September 17–19, 2007 was:

an A/Solomon Islands/3/2006 (H1N1)-like virus;
an A/Brisbane/10/2007 (H3N2)-like virus;
a B/Florida/4/2006-like virus

2008-2009 Northern Hemisphere winter season

The composition of virus vaccines for use in the 2008-2009 Northern Hemisphere influenza season recommended by the World Health Organization on February 14, 2008 was:

an A/Brisbane/59/2007 (H1N1)-like virus;
an A/Brisbane/10/2007 (H3N2)-like virus;
a B/Florida/4/2006-like virus (B/Florida/4/2006 and B/Brisbane/3/2007 (a B/Florida/4/2006-like virus) were used at the time).

As of May 30, 2009: "CDC has antigenically characterized 1,567 seasonal human influenza viruses [947 influenza A (H1), 162 influenza A (H3) and 458 influenza B viruses] collected by U.S. laboratories since October 1, 2008, and 84 novel influenza A (H1N1) viruses. All 947 influenza seasonal A (H1) viruses are related to the influenza A (H1N1) component of the 2008-09 influenza vaccine (A/Brisbane/59/2007). All 162 influenza A (H3N2) viruses are related to the A (H3N2) vaccine component (A/Brisbane/10/2007). All 84 novel influenza A (H1N1) viruses are related to the A/California/07/2009 (H1N1) reference virus selected by WHO as a potential candidate for novel influenza A (H1N1) vaccine. Influenza B viruses currently circulating can be divided into two distinct lineages represented by the B/Yamagata/16/88 and B/Victoria/02/87 viruses. Sixty-one influenza B viruses tested belong to the B/Yamagata lineage and are related to the vaccine strain (B/Florida/04/2006). The remaining 397 viruses belong to the B/Victoria lineage and are not related to the vaccine strain."

2009 Southern Hemisphere winter season

The composition of virus vaccines for use in the 2009 Southern Hemisphere influenza season recommended by the World Health Organization on September 17–19, 2008 was:

an A/Brisbane/59/2007 (H1N1)-like virus;
an A/Brisbane/10/2007 (H3N2)-like virus;
a B/Florida/4/2006-like virus

2009-2010 Northern Hemisphere winter season

The composition of virus vaccines for use in the 2009-2010 Northern Hemisphere influenza season recommended by the World Health Organization on February 12, 2009 was:

an A/Brisbane/59/2007 (H1N1)-like virus;
an A/Brisbane/10/2007 (H3N2)-like virus;
a B/Brisbane/60/2008-like virus.

Since the A/Brisbane/59/2007 (H1N1)-like virus used in the vaccine is an unrelated seasonal strain of influenza, it probably cannot create immunity to the new, non-seasonal strain of influenza A virus subtype H1N1 responsible for the 2009 swine flu outbreak.

2010 Southern Hemisphere winter season

an A/California/7/2009 (H1N1)-like virus;
an A/Perth/16/2009 (H3N2)-like virus;
a B/Brisbane/60/2008-like virus.

The H1N1 strain used in this composition is the same strain used in the 2009 flu pandemic vaccine

2009 flu pandemic vaccine

The 2009 flu pandemic vaccines are the set of influenza vaccines that have been developed to protect against the pandemic H1N1/09 virus. These vaccines either contain inactivated influenza virus, or weakened live virus that cannot cause influenza. The killed vaccine is injected, while the live...

2010-2011 Northern Hemisphere winter season

The composition of virus vaccines for use in the 2010-2011 Northern Hemisphere influenza season recommended by the World Health Organization on February 18, 2010 was:

an A/California/7/2009 (H1N1)-like virus;
an A/Perth/16/2009 (H3N2)-like virus;
a B/Brisbane/60/2008-like virus.

The H1N1 strain used in this composition is the same strain used in the 2009 flu pandemic vaccine

2009 flu pandemic vaccine

2011 Southern Hemisphere winter season

The composition of virus vaccines for use in the 2011 Southern Hemisphere influenza season recommended by the World Health Organization on September 29, 2010 was:

an A/California/7/2009 (H1N1)-like virus;
an A/Perth/16/2009 (H3N2)-like virus;
a B/Brisbane/60/2008-like virus.

The H1N1 strain used in this composition is the same strain used in the 2009 flu pandemic vaccine

2009 flu pandemic vaccine

2011-2012 Northern Hemisphere winter season

The composition of virus vaccines for use in the 2011-2012 Northern Hemisphere influenza season recommended by the World Health Organization on February 17, 2011 was:

an A/California/7/2009 (H1N1)-like virus;
an A/Perth/16/2009 (H3N2)-like virus;
a B/Brisbane/60/2008-like virus.

The H1N1 strain used in this composition is the same strain used in the 2009 flu pandemic vaccine

2009 flu pandemic vaccine

Flu vaccine for nonhumans

"Vaccination in the veterinary world pursues four goals: (i) protection from clinical disease, (ii) protection from infection with virulent virus, (iii) protection from virus excretion, and (iv) serological differentiation of infected from vaccinated animals (so-called DIVA principle). In the field of influenza vaccination, neither commercially available nor experimentally tested vaccines have been shown so far to fulfil all of these requirements."

Horses

Horse

The horse is one of two extant subspecies of Equus ferus, or the wild horse. It is a single-hooved mammal belonging to the taxonomic family Equidae. The horse has evolved over the past 45 to 55 million years from a small multi-toed creature into the large, single-toed animal of today...

s with horse flu

Horse flu

Equine influenza is the disease caused by strains of Influenza A that are enzootic in horse species. Equine influenza occurs globally, and is caused by two main strains of virus: equine-1 and equine-2...

can run a fever, have a dry hacking cough, have a runny nose, and become depressed and reluctant to eat or drink for several days but usually recover in two to three weeks. "Vaccination schedules generally require a primary course of 2 doses, 3–6 weeks apart, followed by boosters at 6–12 month intervals. It is generally recognised that in many cases such schedules may not maintain protective levels of antibody and more frequent administration is advised in high-risk situations."

It is a common requirement at shows in the United Kingdom that horses be vaccinated against equine flu and a vaccination card must be produced; the FEI

International Federation for Equestrian Sports

The Fédération Équestre Internationale or in English, the International Federation for Equestrian Sports, is the international governing body of equestrian sports. It recognizes ten international disciplines...

requires vaccination every six months.

Poultry

Poultry are domesticated birds kept by humans for the purpose of producing eggs, meat, and/or feathers. These most typically are members of the superorder Galloanserae , especially the order Galliformes and the family Anatidae , commonly known as "waterfowl"...

vaccines for bird flu are made on the cheap and are not filtered and purified like human vaccines to remove bits of bacteria or other viruses. They usually contain whole virus, not just hemagglutinin

Hemagglutinin

as in most human flu vaccines. Purification to standards needed for humans is far more expensive than the original creation of the unpurified vaccine from eggs. There is no market for veterinary vaccines that are that expensive. Another difference between human and poultry vaccines is that poultry vaccines are adjuvated

Immunologic adjuvant

with mineral oil, which induces a strong immune reaction but can cause inflammation and abscesses. "Chicken vaccinators who have accidentally jabbed themselves have developed painful swollen fingers or even lost thumbs, doctors said. Effectiveness may also be limited. Chicken vaccines are often only vaguely similar to circulating flu strains — some contain an H5N2

H5N2

H5N2 is a subtype of the species Influenzavirus A .-H5N2 and birds:Low pathogenic avian inluenza H5N2 virus in poultry later gained accentuated virulence in the United States and Mexico...

strain isolated in Mexico years ago. 'With a chicken, if you use a vaccine that's only 85 percent related, you'll get protection,' Dr. Cardona said. 'In humans, you can get a single point mutation, and a vaccine that's 99.99 percent related won't protect you.' And they are weaker [than human vaccines]. 'Chickens are smaller and you only need to protect them for six weeks, because that's how long they live till you eat them,' said Dr. John J. Treanor, a vaccine expert at the University of Rochester. Human seasonal flu vaccines contain about 45 micrograms of antigen, while an experimental A(H5N1

H5N1

Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...

) vaccine contains 180. Chicken vaccines may contain less than 1 microgram. 'You have to be careful about extrapolating data from poultry to humans,' warned Dr. David E. Swayne, director of the agriculture department's Southeast Poultry Research Laboratory. 'Birds are more closely related to dinosaur

Dinosaur

Dinosaurs are a diverse group of animals of the clade and superorder Dinosauria. They were the dominant terrestrial vertebrates for over 160 million years, from the late Triassic period until the end of the Cretaceous , when the Cretaceous–Paleogene extinction event led to the extinction of...

s.'"

Researchers, led by Nicholas Savill of the University of Edinburgh in Scotland, used mathematical models to simulate the spread of H5N1

H5N1

Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...

and concluded that "at least 95 per cent of birds need to be protected to prevent the virus spreading silently. In practice, it is difficult to protect more than 90 per cent of a flock; protection levels achieved by a vaccine are usually much lower than this." The Food and Agriculture Organization of the United Nations has issued recommendations on the prevention and control of avian influenza in poultry, including the use of vaccination.

A filtered and purified Influenza A vaccine for humans is being developed and many countries have recommended it be stockpiled so if an Avian influenza pandemic starts jumping to humans, the vaccine can quickly be administered to avoid loss of life. Avian influenza is sometimes called avian flu, and commonly bird flu.

Pigs

Swine origin influenza virus (SoIV) vaccines are extensively used in the swine industry in Europe and North America. Most swine flu vaccine manufacturers include an H1N1

H1N1

'Influenza A virus is a subtype of influenza A virus and was the most common cause of human influenza in 2009. Some strains of H1N1 are endemic in humans and cause a small fraction of all influenza-like illness and a small fraction of all seasonal influenza. H1N1 strains caused a few percent of...

and an H3N2

H3N2

Influenza A virus subtype H3N2 is a subtype of viruses that cause influenza . H3N2 Viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains...

SoIV strains.

Swine influenza has become a greater problem in recent decades. Evolution

Evolution

Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...

of the virus has resulted in inconsistent responses to traditional vaccines. Standard commercial swine origin flu vaccines are effective in controlling the problem when the virus strains match enough to have significant cross-protection and custom (autogenous) vaccines made from the specific viruses isolated are created and used in the more difficult cases. SoIV vaccine manufacture Novartis paints this picture: "A strain of swine origin influenza virus (SoIV) called H3N2, first identified in the US in 1998, has brought exasperating production losses to swine producers. Abortion storms are a common sign. Sows go off feed for two or three days and run a fever up to 106°F. Mortality in a naïve herd can run as high as 15%."

Dogs

In 2004, Influenza A virus subtype H3N8

H3N8

H3N8 is a subtype of the species Influenza A virus that is endemic in birds, horses and dogs.-Introduction:Equine influenza is a highly contagious respiratorydisease of horses and related animals such as donkeys,...

was discovered to cause canine influenza

Canine influenza

Canine influenza is influenza occurring in canines. Canine influenza is caused by varieties of Influenzavirus A, such as equine influenza virus H3N8, which in 2004 was discovered to cause disease in dogs. Because of the lack of previous exposure to this virus, dogs have no natural immunity to...

. Because of the lack of previous exposure to this virus, dogs have no natural immunity to this virus. However a vaccine is now available.

Computer-assisted vaccine design

A new parameter has been defined to quantify the antigenic distance between two H3N2 influenza strains. This parameter was used to measure antigenic distance between circulating H3N2 strains and the closest vaccine component of the influenza vaccine. For the data between 1971 and 2004, the measure of antigenic distance correlated better with efficacy in humans of the H3N2 influenza A annual vaccine than did current measures of antigenic distance such as phylogenetic sequence analysis or ferret antisera inhibition assays. This measure of antigenic distance could be used to guide the design of the annual flu vaccine. The antigenic distance combined with a multiple-strain avian influenza transmission model was used to study the threat of simultaneous introduction of multiple avian influenza strains. Population at Risk (PaR) can be used to quantify the risk of a flu pandemic and to calculate the improvement that a multiple vaccine offers.

External links

Vaccine Strains vs. Circulating Strains
NHS seasonal flu vaccination campaign NHS flu fighter
History of past WHO seasonal influenza vaccine composition recommendations
Vaccine Research Center Information from NIAID regarding preventative vaccine research studies
About the flu jab (NHS Direct)
World Health Organization's Initiative for Vaccine Research Influenza web page
PandemicFlu.gov
Influenza Strategies for Broad Global Access
PATH's Vaccine Resource Library influenza resources
CDC 2009 H1N1 Influenza Vaccine Supply Status
CDC Vaccine Information Statement Inactivated Inﬂuenza Vaccine
2009-10 Swine Flu Vaccination Clinic Locations in Canada
Read Congressional Research Service (CRS) Reports regarding Influenza and vaccines
Influenza Research Database – Database of influenza genomic sequences and related information.
Health-EU portal EU response to influenza
European Commission - Public Health EU coordination on Pandemic (H1N1) 2009
Centers for Disease Control and Prevention
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...

- Vaccines and Preventable Diseases - Seasonal Influenza (Flu) Vaccination
Centers for Disease Control and Prevention
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...

- Misconceptions about Seasonal Influenza and Influenza Vaccines
Influenza Vaccine (NYTimes / Adam)

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