2009 flu pandemic vaccine
Encyclopedia
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 (killed) influenza virus, or weakened live virus that cannot cause influenza. The killed vaccine is injected, while the live vaccine is given as a nasal spray. Both these types of vaccine are usually produced by growing the virus in chicken eggs. Around three billion doses will be produced annually, with delivery from November 2009.
In studies, the vaccine appears both effective and safe, providing a strong protective immune response and having similar safety profile to the normal seasonal influenza vaccine. However, about 30% of people already have some immunity to the virus, with the vaccine conferring greatest benefit on young people, since many older people are already immune through exposure to similar viruses in the past. The vaccine also provides some cross-protection against the 1918 flu pandemic strain.
Early results (pre-25 December 2009) from an observational cohort of 248,000 individuals in Scotland have shown the vaccine to be effective at preventing H1N1 influenza (95.0% effectiveness [95% confidence intervals (CI) 76.0-100.0]) and influenza related hospital admissions (64.7% [95%CI 12.0-85.8]).
Developing, testing, and manufacturing sufficient quantities of a vaccine is a process that takes many months. According to Keiji Fukuda of the World Health Organization
(WHO), "There's much greater vaccine capacity than there was a few years ago, but there is not enough vaccine capacity to instantly make vaccines for the entire world's population for influenza." Nasal mist version of the vaccine started shipping on October 1, 2009.
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 the body with those same three strains, but in a modified form that cannot cause illness.
LAIV is not recommended for individuals under age 2 or over age 49, but might be comparatively more effective among children over age two.
s, into fertilized chicken eggs. About one to two eggs are needed to make each dose of vaccine. The virus replicates within the allantois
of the embryo, which is the equivalent of the placenta
in mammals. The fluid in this structure is removed and the virus purified from this fluid by methods such as filtration
or centrifugation
. The purified viruses are then inactivated ("killed") with a small amount of a disinfectant. The inactivated virus is treated with detergent to break up the virus into particles, and the broken capsule segments and released proteins are concentrated by centrifugation. The final preparation is suspended in sterile phosphate buffered saline
ready for injection. This vaccine mainly contains the killed virus but might also contain tiny amounts of egg protein and the antibiotics, disinfectant and detergent used in the manufacturing process. In multi-dose versions of the vaccine, the preservative thimerosal is added to prevent growth of bacteria. In some versions of the vaccine used in Europe and Canada, such as Arepanrix and Fluad, an adjuvant
is also added, this contains a fish oil called squalene
, vitamin E
and an emulsifier called polysorbate 80
.
For the live vaccine, the virus is first adapted to grow at 25 °C (77 °F) and then grown at this temperature until it loses the ability to cause illness in humans, which would require the virus to grow at our normal body temperature of 37 °C (98.6 °F). Multiple mutations are needed for the virus to grow at cold temperatures, so this process is effectively irreversible and once the virus has lost virulence
(become "attenuated"), it will not regain the ability to infect people. To make the vaccine, the attenuated virus is grown in chicken eggs as before. The virus-containing fluid is harvested and the virus purified by filtration; this step also removes any contaminating bacteria. The filtered preparation is then diluted into a solution that stabilizes the virus. This solution contains monosodium glutamate
, potassium phosphate
, gelatin
, the antibiotic gentamicin
, and sugar.
A new method of producing influenza virus is used to produce the Novartis
vaccine Optaflu
. In this vaccine the virus is grown in cell culture
instead of in eggs. This method is faster than the classic egg-based system and produces a purer final product. Importantly, there are no traces of egg proteins in the final product, so the vaccine is safe for people with egg allergies.
(CDC) characterized over 80 new H1N1 viruses that may be used in a vaccine.
. The news site added that although vaccine makers would be ready to switch to making a swine flu vaccine, many questions remained unanswered, including: "Should we really make a swine flu vaccine? Should we base a vaccine on the current virus, since flu viruses change rapidly? Vaccine against the current virus might be far less effective against a changed virus - should we wait to see if the virus changes? If vaccine production doesn't start soon, swine flu vaccine won't be ready when it's needed."
The costs of producing a vaccine also became an issue, with some U.S. lawmakers questioning whether a new vaccine was worth the unknown benefits. Representatives Phil Gingrey
and Paul Broun
, for instance, were not convinced that the U.S. should spend up to USD
$2 billion to produce one, with Gingrey stating "We can't let all of our spending and our reaction be media-driven in responding to a panic so that we don't get Katrina-ed. ... It's important because what we are talking about as we discuss the appropriateness of spending $2 billion to produce a vaccine that may never be used — that is a very important decision that our country has to make." In fact, a Fairleigh Dickinson University
PublicMind poll found in October 2009 that a majority (62%) of New Jerseyans were not planning on getting the vaccine at all.
Before the pandemic was declared, the WHO said that if a pandemic was declared it would attempt to make sure that a substantial amount of vaccine was available for the benefit of developing countries. Vaccine makers and countries with standing orders, such as the U.S. and a number of European countries, would be asked, according to WHO officials, "to share with developing countries from the moment the first batches are ready if an H1N1 vaccine is made" for a pandemic strain. The global body stated that it wanted companies to donate at least 10% of their production or offer reduced prices for poor countries that could otherwise be left without vaccines if there is a sudden surge in demand.
Gennady Onishchenko, Russia
's chief doctor, said on June 2, 2009 that swine flu was not aggressive enough to cause a worldwide pandemic, noting that the current mortality rate of confirmed cases was 1.6% in Mexico
and only 0.1% in the United States. He stated at a press conference, "So far it is unclear if we need to use vaccines against the flu because the virus that is now circulating throughout Europe
and North America
does not have a pandemic nature." In his opinion, a vaccine could be produced, but said that preparing a vaccine now would be considered "practice," since the world would soon need a new vaccine against a new virus. "What's 16,000 sick people? During any flu season, some 10,000 a day become ill in Moscow
alone," he said.
told reporters "These are enormously complicated questions, and they are not something that anyone can make in a single meeting." Most flu vaccine companies can not make both seasonal flu vaccine and pandemic flu vaccine at the same time. Production takes months and it is impossible to switch halfway through if health officials make a mistake. If the swine flu mutates, scientists aren't sure how effective a vaccine made now from the current strain will remain. Rather than wait on the WHO decision, however, some countries in Europe have decided to go ahead with early vaccine orders.
On May 20, 2009, AP reported: "Manufacturers won't be able to start making the [swine flu] vaccine until mid-July at the earliest, weeks later than previous predictions, according to an expert panel convened by WHO. It will then take months to produce the vaccine in large quantities. The swine flu virus is not growing very fast in laboratories, making it difficult for scientists to get the key ingredient they need for a vaccine, the 'seed stock' from the virus [...] In any case, mass producing a pandemic vaccine would be a gamble, as it would take away manufacturing capacity for the seasonal flu vaccine for the flu that kills up to 500,000 people each year. Some experts have wondered whether the world really needs a vaccine for an illness that so far appears mild."
Another option proposed by the CDC was an "earlier rollout of seasonal vaccine," according to the CDC's Dr. Daniel Jernigan. He said the CDC would work with vaccine manufacturers and experts to see if that would be possible and desirable. Flu vaccination usually starts in September in the United States and peaks in November. Some vaccine experts agree it would be better to launch a second round of vaccinations against the new H1N1 strain instead of trying to add it to the seasonal flu vaccine or replacing one of its three components with the new H1N1 virus.
The Australia
n company CSL
said that they were developing a vaccine for the swine flu and predicted that a suitable vaccine would be ready by August. However, John Sterling, Editor in Chief of Genetic Engineering & Biotechnology News, said on June 2, "It can take five or six months to come up with an entirely novel influenza vaccine. There is a great deal of hope that biotech and pharma companies might be able to have something ready sooner."
a vaccine for H1N1/09
was expected to be available starting in November 2009, with production of three billion doses per year. It was expected that two doses would be needed to provide sufficient protection, but tests indicated that one dose would be sufficient for adults.
GlaxoSmithKline
produced a vaccine made by growing the virus in hens' eggs, then breaking and deactivating the virus,
and Baxter International
produced a vaccine made in cell culture, suitable for those who have an egg allergy. The vaccines have been approved for use in the European Union
.
' MF59
candidate in July 2009, at which time phase II trials of CSL's candidate CSL425 vaccine were planned to start in August 2009, but had not begun recruiting. Sanofi Pasteur
's candidate inactivated H1N1 had several phase II trials planned , but had not begun recruiting.
News coverage conflicted with this information, as Australian trials of the CSL candidate were announced as having started on 21 July, and the Chinese government announced the start of trials of the Hualan Biological Engineering candidate.
Pandemrix
, made by GlaxoSmithKline
(GSK), and Focetria, made by Novartis
were approved by the European Medicines Agency
on 25 September 2009, and Celvapan, made by Baxter was approved the following week. The first comparative clinical study of both vaccines started on children in the United Kingdom
on 25 September 2009.
GSK announced results from clinical trials assessing the use of Pandemrix in children, adults, and the elderly. A 2009 trial examined the safety and efficacy of two different doses of the split-virus vaccine, and was published in The New England Journal of Medicine. The vaccine used in the trail was prepared by CSL Biotherapies in chicken eggs, in the same way as the seasonal vaccine. A robust immune response was produced in over 90% of patients after a single dose of either 15 or 30 μg of antigen. This study suggested that the current recommendation for two doses of vaccine are overkill and that a single dose is quite sufficient.
Arepanrix, an AS03
-Adjuvanted
H1N1 Pandemic Influenza Vaccine similar to Pandemrix and also made by GSK, was authorized by Canada
's Minister of Health on 21 October 2009.
(NIH) concluded that the 2009 H1N1 ("swine flu") vaccine has a safety profile similar to that of seasonal vaccine.
In an initial clinical trial in Australia, non-serious adverse events were reported by about half of the 240 people vaccinated, with these events including tenderness and pain at the site of injection, headache, malaise, and muscle pain. Two people had more severe events, with a much longer spell of nausea, muscle pain and malaise that lasted several days. The authors stated that the frequency and severity of these adverse events were similar to those normally seen with seasonal influenza vaccines. A second trial involved 2,200 people ranging from 3 to 77 years of age. In this study no patients reported serious adverse events, with the most commonly observed events being pain at the injection site and fever, which occurred in 10-25% of people. Although this trial followed up patients individually, the Government has been criticized for relying on voluntary reporting for post-vaccination evaluation in other circumstances, since this is "unlikely to accurately measure the percentage of people who get adverse effect".
, the World Health Organization (WHO) said that 65 million doses of vaccine had been administered and that it had a similar safety profile to the seasonal flu vaccine, with no significant differences in the adverse events produced by the different types of vaccine. There has been one report of an adverse event per 10,000 doses of vaccine, with only five percent of these adverse events being serious, an overall rate of serious events of one in 200,000 doses.
In Canada
, after 6.6 million doses of vaccine had been distributed between October 21 and November 7, there were reports of mild adverse events in 598 people vaccinated including: nausea, dizziness, headache, fever, vomiting, and swelling or soreness at the injection site. There were reports of tingling lips or tongue, difficulty breathing, hives, and skin rashes. Thirty six people had serious adverse events, including anaphylaxis
and febrile convulsions. The rate of serious adverse events is one in 200,000 doses distributed, which according to Canada's chief public health officer, is less than expected for the seasonal flu vaccine. GlaxoSmithKline recalled a batch of vaccine in Canada after it appeared to cause higher rates of adverse events than other batches.
In the USA 46 million doses had been distributed and 3182 adverse events were reported. The CDC stated that the "vast majority" were mild, with about one serious adverse event in 260,000 doses.
In Japan
around 15 million people had been vaccinated by 31 December 2009. 1,900 cases of side effects and 104 cases of death were reported from medical institutions. The health ministry announced that it will conduct epidemiologic investigation.
In France
, around five million people had been vaccinated by 30 December 2009. 2,657 cases of side effects, eight cases of intrauterine death and five cases of miscarriages were reported after vaccination by afssaps.
Rare potential adverse events are temporary bleeding disorders and Guillain-Barré syndrome
(GBS), a serious condition involving the peripheral nervous system
, from which most patients recovery fully within a few months to a year. Some studies have indicated that influenza-like illness is itself associated with an increased risk of GBS, suggesting that vaccination might indirectly protect against the disorder by protecting against flu. According to Marie-Paule Kieny of WHO assessing the side-effects of large-scale influenza vaccination is complicated by the fact that in any large population a few people will become ill and die at any time. For example in any six-week period in the UK six sudden deaths from unknown causes and 22 cases of Guillain-Barré syndrome would be expected, so if everyone in the UK were vaccinated, this background rate of illness and death would continue as normal and some people would die simply by chance soon after the vaccination.
Some scientists have reported concerns about the longer-term effects of the vaccine. For instance, Sucharit Bhakdi, professor of medical microbiology at the Johannes Gutenberg University of Mainz in Germany, wrote in the journal, Medical Microbiology and Immunology, of the possibility that immune stimulation by vaccines or any other cause might worsen pre-existing heart disease. Chris Shaw, a neuroscientist at the University of British Columbia, expressed concern that serious side-effects may not appear immediately; he said it took five to ten years to see most of the Gulf War syndrome
outcomes.
The CDC states that most studies on modern influenza vaccines have seen no link with GBS, Although one review gives an incidence of about one case per million vaccinations, a large study in China, reported in The New England Journal of Medicine covering close to 100 million doses of H1N1 flu vaccine found only eleven cases of Guillain-Barre syndrome
, actually lower than the normal rate of the disease in China, and no other notable side effects.
. For example, Newsweek states that some chain e-mails make false claims about squalene
(shark liver oil) in vaccines. The New York Times also notes that anti-vaccine groups have spread "dire warnings" about formulations of the vaccine that contain squalene as an adjuvant
. An adjuvant is a substance that boosts the body's immune response, thereby stretching the supply of the vaccine and helping immunize elderly people with a weak immune system. Squalene is a normal part of the human body, made in the liver and circulating in the blood, and is also found in many foods, such as egg
s and olive oil
. None of the formulations of vaccine used in the US contain squalene, or any other adjuvant. However, some European and Canadian formulations do contain 25 μg of squalene per dose, which is roughly the amount found in a drop of olive oil. Some animal experiments have suggested that squalene might be linked to autoimmune disorders. although others suggest squalene might protect people against cancer
.
Squalene-based adjuvants have been used in Europe
an influenza vaccines since 1997, with about 22 million doses administered over the past twelve years. The WHO states that no severe side effects have been associated with these vaccines, although they can produce mild inflammation at the site of injection. The safety of squalene-containing influenza vaccines have also been tested in two separate clinical trials, one with healthy non-elderly people, and one with elderly people, in both trials the vaccine was safe and well-tolerated, with only weak side-effects such as mild pain at the injection site. A 2009 meta-analysis
brought together data from 64 clinical trials of influenza vaccines with the squalene-containing adjuvant MF59 and compared them to the effects of vaccines with no adjuvant. The analysis reported that the adjuvanted vaccines were associated with slightly lower risks of chronic diseases, but that neither type of vaccines altered the normal rate of autoimmune diseases; the authors concluded that their data "supports the good safety profile associated with MF59-adjuvanted influenza vaccines and suggests there may be a clinical benefit over non-MF59-containing vaccines". A 2004 review of the effects of adjuvants on mice and humans concluded that "despite numerous case reports on vaccination induced autoimmunity, most epidemiological studies failed to confirm the association and the risk appears to be extremely low or non-existent", although the authors noted that the possibility that adjuvants might cause damaging immune reactions in a few susceptible people has not been completely ruled out. A 2009 review of oil-based adjuvants in influenza vaccines stated that this type of adjuvant "neither stimulates antibodies against squalene oil naturally produced by the humans body nor enhances titers of preexisting antibodies to squalene" and that these formulations did not raise any safety concerns.
A paper published in 2000 suggested that squalene might have caused of Gulf War syndrome
by producing anti-squalene antibodies, although other scientists stated that it was uncertain if the methods used were actually capable of detecting these antibodies. A 2009 U.S. Department of Defense study comparing healthy Navy personnel to those suffering from Gulf War syndrome was published in the journal Vaccine, this used a validated test for these antibodies and found no link between the presence of the antibodies and illness, with about half of both groups having these antibodies and no correlation between symptoms and antibodies. Furthermore, none of the vaccines given to US troops during the Gulf war actually contained any squalene adjuvants.
(also known as thimerosal), a mercury
compound that prevents contamination when the vial is used repeatedly. Single-dose versions and the live vaccine do not contain this preservative. In the U.S., one dose from a multi-dose vial contains approximately 25 micrograms of mercury, a bit less than a typical tuna fish sandwich
. In Canada, different variants contain five and 50 micrograms of thimerosal per dose. The use of thiomersal has been controversial
, with claims that it can cause autism
and other developmental disorder
s. The U.S. Institute of Medicine
examined these claims and concluded in 2004 that the evidence did not support any link between vaccines and autism. Other reviews came to similar conclusions, with a 2006 review in the Canadian Journal of Neurological Sciences stating that there is no convincing evidence to support the claim that thimerosal has a causal role in autism, and a 2009 review in the journal Clinical Infectious Diseases
stating that claims that mercury can cause autism are "biologically implausible". The U.K. National Health Service
stated in 2003 that "There is no evidence of long-term adverse effects due to the exposure levels of thiomersal in vaccines." The World Health Organization
concluded that there is "no evidence of toxicity in infants, children or adults exposed to thiomersal in vaccines". Indeed, in 2008 a review noted that even though thiomersal was removed from all US childhood vaccines in 2001, this has not changed the number of autism diagnoses, which are still increasing.
being caused by the vaccinations. Dystonia is extremely rare. Due to the very low numbers of cases, dystonia is poorly-understood. There were only five cases noted that might have been associated with influenza vaccinations over a span of eighteen years. In one recent case, a woman noted flu-like symptoms, followed by difficulties with movement and speech starting ten days after a seasonal influenza vaccination. However the Dystonia Medical Research Foundation stated that it is unlikely that the symptoms in this case were actually dystonia and stated that there has "never been a validated case of dystonia resulting from a flu shot".
voluntarily recalled about 800,000 doses of vaccine meant for children between the ages of six months and 35 months. The company and the Centers for Disease Control and Prevention
(CDC) emphasized that the recall was not prompted by safety concerns, and that even though the vaccine is not quite as potent as it is supposed to be, children who received it do not need to be immunized again. The CDC emphasized that there is no danger for any child who received the recalled vaccine. When asked what parents should do, CDC spokesman Tom Skinner said, "absolutely nothing." He said if children receive this vaccine, they will be fine.
issued the following recommendations on who should be vaccinated (order is not in priority):
In addition, the CDC recommends
policy is to provide vaccine in this order of priority:
This excludes the large majority of individuals aged six months to 24 years, a group for which the CDC recommends vaccination.
The NHS notes that:
The United Kingdom began its administration program October 21, 2009. UK Soldiers serving in Afghanistan
will also be offered vaccination.
is planning to examine if it overreacted to the H1N1 outbreak.
While it has been suggested that compulsory vaccination may be needed to control a pandemic, many countries do not have a legal framework that would allow this. The only populations easily compelled to accept vaccination are military personnel (who can be given routine vaccinations as part of their service obligations), health care personnel (who can be required to be vaccinated to protect patients), and school children, who (under United States constitutional law) could be required to be vaccinated as a condition of attending school.
In August 2010, the Daily Mail
printed an article that stated that "a third of the experts advising the World Health Organisation about the swine flu pandemic had ties to drugs firms" and that of the 20 members of the Scientific Advisory Group for Emergencies, which advised the British Government on swine flu, 11 had done work for the pharmaceutical industry or were linked to it through their universities. A spokesman for the WHO is stated as having "denied that the experts' work gave rise to a conflict of interest".
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:...
. These vaccines either contain inactivated (killed) influenza virus, or weakened live virus that cannot cause influenza. The killed vaccine is injected, while the live vaccine is given as a nasal spray. Both these types of vaccine are usually produced by growing the virus in chicken eggs. Around three billion doses will be produced annually, with delivery from November 2009.
In studies, the vaccine appears both effective and safe, providing a strong protective immune response and having similar safety profile to the normal seasonal influenza vaccine. However, about 30% of people already have some immunity to the virus, with the vaccine conferring greatest benefit on young people, since many older people are already immune through exposure to similar viruses in the past. The vaccine also provides some cross-protection against the 1918 flu pandemic strain.
Early results (pre-25 December 2009) from an observational cohort of 248,000 individuals in Scotland have shown the vaccine to be effective at preventing H1N1 influenza (95.0% effectiveness [95% confidence intervals (CI) 76.0-100.0]) and influenza related hospital admissions (64.7% [95%CI 12.0-85.8]).
Developing, testing, and manufacturing sufficient quantities of a vaccine is a process that takes many months. According to Keiji Fukuda of 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...
(WHO), "There's much greater vaccine capacity than there was a few years ago, but there is not enough vaccine capacity to instantly make vaccines for the entire world's population for influenza." Nasal mist version of the vaccine started shipping on October 1, 2009.
Types of vaccine
Two types of influenza vaccines are available:- TIV (flu shot (injectionInjection (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/H3N2H3N2Influenza 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) inactivated (killed) vaccine) or - LAIV (nasal spray (mist) of live attenuated influenza vaccineLive attenuated influenza vaccineLive 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 the body with those same three strains, but in a modified form that cannot cause illness.
LAIV is not recommended for individuals under age 2 or over age 49, but might be comparatively more effective among children over age two.
Manufacturing methods
For the inactivated vaccines, the virus is grown by injecting it, along with some antibioticAntibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
s, into fertilized chicken eggs. About one to two eggs are needed to make each dose of vaccine. The virus replicates within the allantois
Allantois
Allantois is a part of a developing animal conceptus . It helps the embryo exchange gases and handle liquid waste....
of the embryo, which is the equivalent of the placenta
Placenta
The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...
in mammals. The fluid in this structure is removed and the virus purified from this fluid by methods such as filtration
Filtration
Filtration is commonly the mechanical or physical operation which is used for the separation of solids from fluids by interposing a medium through which only the fluid can pass...
or centrifugation
Centrifugation
Centrifugation is a process that involves the use of the centrifugal force for the sedimentation of mixtures with a centrifuge, used in industry and in laboratory settings. More-dense components of the mixture migrate away from the axis of the centrifuge, while less-dense components of the mixture...
. The purified viruses are then inactivated ("killed") with a small amount of a disinfectant. The inactivated virus is treated with detergent to break up the virus into particles, and the broken capsule segments and released proteins are concentrated by centrifugation. The final preparation is suspended in sterile phosphate buffered saline
Phosphate buffered saline
Phosphate buffered saline is a buffer solution commonly used in biological research. It is a water-based salt solution containing sodium chloride, sodium phosphate, and, in some formulations, potassium chloride and potassium phosphate. The buffer's phosphate groups help to maintain a constant pH...
ready for injection. This vaccine mainly contains the killed virus but might also contain tiny amounts of egg protein and the antibiotics, disinfectant and detergent used in the manufacturing process. In multi-dose versions of the vaccine, the preservative thimerosal is added to prevent growth of bacteria. In some versions of the vaccine used in Europe and Canada, such as Arepanrix and Fluad, an 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...
is also added, this contains a fish oil called squalene
Squalene
Squalene is a natural organic compound originally obtained for commercial purposes primarily from shark liver oil, though plant sources are used as well, including amaranth seed, rice bran, wheat germ, and olives. All plants and animals produce squalene, including humans...
, vitamin E
Vitamin E
Vitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols. There are many different forms of vitamin E, of which γ-tocopherol is the most common in the North American diet. γ-Tocopherol can be found in corn oil, soybean oil, margarine and dressings...
and an emulsifier called polysorbate 80
Polysorbate 80
Polysorbate 80 is a nonionic surfactant and emulsifier derived from polyethoxylated sorbitan and oleic acid, and is often used in foods. Polysorbate 80 is a viscous, water-soluble yellow liquid...
.
For the live vaccine, the virus is first adapted to grow at 25 °C (77 °F) and then grown at this temperature until it loses the ability to cause illness in humans, which would require the virus to grow at our normal body temperature of 37 °C (98.6 °F). Multiple mutations are needed for the virus to grow at cold temperatures, so this process is effectively irreversible and once the virus has lost virulence
Virulence
Virulence is by MeSH definition the degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenicity of an organism - its ability to cause disease - is determined by its...
(become "attenuated"), it will not regain the ability to infect people. To make the vaccine, the attenuated virus is grown in chicken eggs as before. The virus-containing fluid is harvested and the virus purified by filtration; this step also removes any contaminating bacteria. The filtered preparation is then diluted into a solution that stabilizes the virus. This solution contains monosodium glutamate
Monosodium glutamate
Monosodium glutamate, also known as sodium glutamate or MSG, is the sodium salt of glutamic acid, one of the most abundant naturally occurring non-essential amino acids....
, potassium phosphate
Potassium phosphate
Potassium phosphate is a generic term for the salts of potassium and phosphate ions including:* Monopotassium phosphate * Dipotassium phosphate * Tripotassium phosphate...
, gelatin
Gelatin
Gelatin is a translucent, colorless, brittle , flavorless solid substance, derived from the collagen inside animals' skin and bones. It is commonly used as a gelling agent in food, pharmaceuticals, photography, and cosmetic manufacturing. Substances containing gelatin or functioning in a similar...
, the antibiotic gentamicin
Gentamicin
Gentamicin is an aminoglycoside antibiotic, used to treat many types of bacterial infections, particularly those caused by Gram-negative organisms. However, gentamicin is not used for Neisseria gonorrhoeae, Neisseria meningitidis or Legionella pneumophila...
, and sugar.
A new method of producing influenza virus is used to produce the Novartis
Novartis
Novartis International AG is a multinational pharmaceutical company based in Basel, Switzerland, ranking number three in sales among the world-wide industry...
vaccine 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...
. In this vaccine the virus is grown in cell culture
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,...
instead of in eggs. This method is faster than the classic egg-based system and produces a purer final product. Importantly, there are no traces of egg proteins in the final product, so the vaccine is safe for people with egg allergies.
Previous seasonal vaccine production
The WHO recommended before the H1N1/09 outbreak that vaccines for the Northern Hemisphere's 2009–2010 flu season contain an A(H1N1)-like virus, and stocks have been made. However, the strain of H1N1 in the seasonal flu vaccine is different from the new pandemic strain H1N1/09 and offers no immunity against it. The US Centers for Disease Control and PreventionCenters 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) characterized over 80 new H1N1 viruses that may be used in a vaccine.
Questions
There was concern in mid-2009 that, should a second, deadlier wave of this new H1N1 strain appear during the northern autumn of 2009, producing pandemic vaccines ahead of time could turn out to be a serious waste of resources as the vaccine might not be effective against it, and there would also be a shortage of seasonal flu vaccine available if production facilities were switched to the new vaccine. Seasonal flu vaccine was being made as of May 2009, according to WebMDWebMD
WebMD is an American corporation which provides health information services. It was founded in 1996 by Jim Clark and Pavan Nigam as Healthscape, later Healtheon, and then acquired WebMD in 1999 to form Healtheon/WebMD...
. The news site added that although vaccine makers would be ready to switch to making a swine flu vaccine, many questions remained unanswered, including: "Should we really make a swine flu vaccine? Should we base a vaccine on the current virus, since flu viruses change rapidly? Vaccine against the current virus might be far less effective against a changed virus - should we wait to see if the virus changes? If vaccine production doesn't start soon, swine flu vaccine won't be ready when it's needed."
The costs of producing a vaccine also became an issue, with some U.S. lawmakers questioning whether a new vaccine was worth the unknown benefits. Representatives Phil Gingrey
Phil Gingrey
John Phillip "Phil" Gingrey, is the U.S. Representative for , serving since 2003. He is a member of the Republican Party. The district is located in the northwestern suburbs of Atlanta.-Early life, education and career:...
and Paul Broun
Paul Broun
Paul Collins Broun, Jr. is the U.S. Representative for , serving since 2007. He is a member of the Republican Party and the Tea Party Caucus.-Early life, education and career:...
, for instance, were not convinced that the U.S. should spend up to USD
United States dollar
The United States dollar , also referred to as the American dollar, is the official currency of the United States of America. It is divided into 100 smaller units called cents or pennies....
$2 billion to produce one, with Gingrey stating "We can't let all of our spending and our reaction be media-driven in responding to a panic so that we don't get Katrina-ed. ... It's important because what we are talking about as we discuss the appropriateness of spending $2 billion to produce a vaccine that may never be used — that is a very important decision that our country has to make." In fact, a Fairleigh Dickinson University
Fairleigh Dickinson University
Fairleigh Dickinson University is a private university founded as a junior college in 1942. It now has several campuses located in New Jersey, Canada, and the United Kingdom.-Description:...
PublicMind poll found in October 2009 that a majority (62%) of New Jerseyans were not planning on getting the vaccine at all.
Before the pandemic was declared, the WHO said that if a pandemic was declared it would attempt to make sure that a substantial amount of vaccine was available for the benefit of developing countries. Vaccine makers and countries with standing orders, such as the U.S. and a number of European countries, would be asked, according to WHO officials, "to share with developing countries from the moment the first batches are ready if an H1N1 vaccine is made" for a pandemic strain. The global body stated that it wanted companies to donate at least 10% of their production or offer reduced prices for poor countries that could otherwise be left without vaccines if there is a sudden surge in demand.
Gennady Onishchenko, Russia
Russia
Russia or , officially known as both Russia and the Russian Federation , is a country in northern Eurasia. It is a federal semi-presidential republic, comprising 83 federal subjects...
's chief doctor, said on June 2, 2009 that swine flu was not aggressive enough to cause a worldwide pandemic, noting that the current mortality rate of confirmed cases was 1.6% in Mexico
Mexico
The United Mexican States , commonly known as Mexico , is a federal constitutional republic in North America. It is bordered on the north by the United States; on the south and west by the Pacific Ocean; on the southeast by Guatemala, Belize, and the Caribbean Sea; and on the east by the Gulf of...
and only 0.1% in the United States. He stated at a press conference, "So far it is unclear if we need to use vaccines against the flu because the virus that is now circulating throughout 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 North America
North America
North America is a continent wholly within the Northern Hemisphere and almost wholly within the Western Hemisphere. It is also considered a northern subcontinent of the Americas...
does not have a pandemic nature." In his opinion, a vaccine could be produced, but said that preparing a vaccine now would be considered "practice," since the world would soon need a new vaccine against a new virus. "What's 16,000 sick people? During any flu season, some 10,000 a day become ill in Moscow
Moscow
Moscow is the capital, the most populous city, and the most populous federal subject of Russia. The city is a major political, economic, cultural, scientific, religious, financial, educational, and transportation centre of Russia and the continent...
alone," he said.
Production timelines
After a meeting with the WHO on May 14, 2009, pharmaceutical companies said they were ready to begin making a swine flu vaccine. According to news reports, the WHO's experts will present recommendations to WHO Director-General Margaret Chan, who was expected to issue advice to vaccine manufacturers and the Sixty-second World Health Assembly. WHO's Keiji FukudaKeiji Fukuda
Keiji Fukuda is an American physician with expertise in influenza epidemiology. In March 2009, Fukuda was appointed Assistant Director-General for Health, Security and Environment ad interim for the World Health Organization and as of September 2010, he holds this position permanently...
told reporters "These are enormously complicated questions, and they are not something that anyone can make in a single meeting." Most flu vaccine companies can not make both seasonal flu vaccine and pandemic flu vaccine at the same time. Production takes months and it is impossible to switch halfway through if health officials make a mistake. If the swine flu mutates, scientists aren't sure how effective a vaccine made now from the current strain will remain. Rather than wait on the WHO decision, however, some countries in Europe have decided to go ahead with early vaccine orders.
On May 20, 2009, AP reported: "Manufacturers won't be able to start making the [swine flu] vaccine until mid-July at the earliest, weeks later than previous predictions, according to an expert panel convened by WHO. It will then take months to produce the vaccine in large quantities. The swine flu virus is not growing very fast in laboratories, making it difficult for scientists to get the key ingredient they need for a vaccine, the 'seed stock' from the virus [...] In any case, mass producing a pandemic vaccine would be a gamble, as it would take away manufacturing capacity for the seasonal flu vaccine for the flu that kills up to 500,000 people each year. Some experts have wondered whether the world really needs a vaccine for an illness that so far appears mild."
Another option proposed by the CDC was an "earlier rollout of seasonal vaccine," according to the CDC's Dr. Daniel Jernigan. He said the CDC would work with vaccine manufacturers and experts to see if that would be possible and desirable. Flu vaccination usually starts in September in the United States and peaks in November. Some vaccine experts agree it would be better to launch a second round of vaccinations against the new H1N1 strain instead of trying to add it to the seasonal flu vaccine or replacing one of its three components with the new H1N1 virus.
The 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...
n company CSL
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...
said that they were developing a vaccine for the swine flu and predicted that a suitable vaccine would be ready by August. However, John Sterling, Editor in Chief of Genetic Engineering & Biotechnology News, said on June 2, "It can take five or six months to come up with an entirely novel influenza vaccine. There is a great deal of hope that biotech and pharma companies might be able to have something ready sooner."
a vaccine for 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:...
was expected to be available starting in November 2009, with production of three billion doses per year. It was expected that two doses would be needed to provide sufficient protection, but tests indicated that one dose would be sufficient for adults.
GlaxoSmithKline
GlaxoSmithKline
GlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom...
produced a vaccine made by growing the virus in hens' eggs, then breaking and deactivating the virus,
and Baxter International
Baxter International
Baxter International Inc. , is an American health care company with headquarters in Deerfield, Illinois. The company primarily focuses on products to treat hemophilia, kidney disease, immune disorders and other chronic and acute medical conditions...
produced a vaccine made in cell culture, suitable for those who have an egg allergy. The vaccines have been approved for use in 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...
.
Testing
Initial Phase I human testing began with NovartisNovartis
Novartis International AG is a multinational pharmaceutical company based in Basel, Switzerland, ranking number three in sales among the world-wide industry...
' MF59
MF59
MF59 is an immunologic adjuvant that uses squalene. It is Novartis' proprietary adjuvant that is added to influenza vaccines to help stimulate the human body's immune response through production of CD4 memory cells. MF59 is the first oil-in-water influenza vaccine adjuvant to be commercialized in...
candidate in July 2009, at which time phase II trials of CSL's candidate CSL425 vaccine were planned to start in August 2009, but had not begun recruiting. 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 candidate inactivated H1N1 had several phase II trials planned , but had not begun recruiting.
News coverage conflicted with this information, as Australian trials of the CSL candidate were announced as having started on 21 July, and the Chinese government announced the start of trials of the Hualan Biological Engineering candidate.
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....
, made by GlaxoSmithKline
GlaxoSmithKline
GlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom...
(GSK), and Focetria, made 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...
were approved by the European Medicines Agency
European Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
on 25 September 2009, and Celvapan, made by Baxter was approved the following week. The first comparative clinical study of both vaccines started on children in 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...
on 25 September 2009.
GSK announced results from clinical trials assessing the use of Pandemrix in children, adults, and the elderly. A 2009 trial examined the safety and efficacy of two different doses of the split-virus vaccine, and was published in The New England Journal of Medicine. The vaccine used in the trail was prepared by CSL Biotherapies in chicken eggs, in the same way as the seasonal vaccine. A robust immune response was produced in over 90% of patients after a single dose of either 15 or 30 μg of antigen. This study suggested that the current recommendation for two doses of vaccine are overkill and that a single dose is quite sufficient.
Arepanrix, an AS03
AS03
AS03 is the trade name for a squalene-based immunologic adjuvant used in various vaccine products by GlaxoSmithKline...
-Adjuvanted
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...
H1N1 Pandemic Influenza Vaccine similar to Pandemrix and also made by GSK, was authorized by Canada
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...
's Minister of Health on 21 October 2009.
Adverse events
A review by the U.S. National Institutes of HealthNational 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...
(NIH) concluded that the 2009 H1N1 ("swine flu") vaccine has a safety profile similar to that of seasonal vaccine.
In an initial clinical trial in Australia, non-serious adverse events were reported by about half of the 240 people vaccinated, with these events including tenderness and pain at the site of injection, headache, malaise, and muscle pain. Two people had more severe events, with a much longer spell of nausea, muscle pain and malaise that lasted several days. The authors stated that the frequency and severity of these adverse events were similar to those normally seen with seasonal influenza vaccines. A second trial involved 2,200 people ranging from 3 to 77 years of age. In this study no patients reported serious adverse events, with the most commonly observed events being pain at the injection site and fever, which occurred in 10-25% of people. Although this trial followed up patients individually, the Government has been criticized for relying on voluntary reporting for post-vaccination evaluation in other circumstances, since this is "unlikely to accurately measure the percentage of people who get adverse effect".
, the World Health Organization (WHO) said that 65 million doses of vaccine had been administered and that it had a similar safety profile to the seasonal flu vaccine, with no significant differences in the adverse events produced by the different types of vaccine. There has been one report of an adverse event per 10,000 doses of vaccine, with only five percent of these adverse events being serious, an overall rate of serious events of one in 200,000 doses.
In Canada
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...
, after 6.6 million doses of vaccine had been distributed between October 21 and November 7, there were reports of mild adverse events in 598 people vaccinated including: nausea, dizziness, headache, fever, vomiting, and swelling or soreness at the injection site. There were reports of tingling lips or tongue, difficulty breathing, hives, and skin rashes. Thirty six people had serious adverse events, including anaphylaxis
Anaphylaxis
Anaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure...
and febrile convulsions. The rate of serious adverse events is one in 200,000 doses distributed, which according to Canada's chief public health officer, is less than expected for the seasonal flu vaccine. GlaxoSmithKline recalled a batch of vaccine in Canada after it appeared to cause higher rates of adverse events than other batches.
In the USA 46 million doses had been distributed and 3182 adverse events were reported. The CDC stated that the "vast majority" were mild, with about one serious adverse event in 260,000 doses.
In 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...
around 15 million people had been vaccinated by 31 December 2009. 1,900 cases of side effects and 104 cases of death were reported from medical institutions. The health ministry announced that it will conduct epidemiologic investigation.
In France
France
The French Republic , The French Republic , The French Republic , (commonly known as France , is a unitary semi-presidential republic in Western Europe with several overseas territories and islands located on other continents and in the Indian, Pacific, and Atlantic oceans. Metropolitan France...
, around five million people had been vaccinated by 30 December 2009. 2,657 cases of side effects, eight cases of intrauterine death and five cases of miscarriages were reported after vaccination by afssaps.
Rare potential adverse events are temporary bleeding disorders and 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...
(GBS), a serious condition involving the peripheral nervous system
Peripheral nervous system
The peripheral nervous system consists of the nerves and ganglia outside of the brain and spinal cord. The main function of the PNS is to connect the central nervous system to the limbs and organs. Unlike the CNS, the PNS is not protected by the bone of spine and skull, or by the blood–brain...
, from which most patients recovery fully within a few months to a year. Some studies have indicated that influenza-like illness is itself associated with an increased risk of GBS, suggesting that vaccination might indirectly protect against the disorder by protecting against flu. According to Marie-Paule Kieny of WHO assessing the side-effects of large-scale influenza vaccination is complicated by the fact that in any large population a few people will become ill and die at any time. For example in any six-week period in the UK six sudden deaths from unknown causes and 22 cases of Guillain-Barré syndrome would be expected, so if everyone in the UK were vaccinated, this background rate of illness and death would continue as normal and some people would die simply by chance soon after the vaccination.
Some scientists have reported concerns about the longer-term effects of the vaccine. For instance, Sucharit Bhakdi, professor of medical microbiology at the Johannes Gutenberg University of Mainz in Germany, wrote in the journal, Medical Microbiology and Immunology, of the possibility that immune stimulation by vaccines or any other cause might worsen pre-existing heart disease. Chris Shaw, a neuroscientist at the University of British Columbia, expressed concern that serious side-effects may not appear immediately; he said it took five to ten years to see most of the Gulf War syndrome
Gulf War syndrome
Gulf War syndrome or Gulf War illness describes a medical condition that affected veterans and civilians who were near conflicts during or downwind of chemical weapons depot demolition, after the 1991 Gulf War. A wide range of acute and chronic symptoms have included fatigue, musculoskeletal...
outcomes.
The CDC states that most studies on modern influenza vaccines have seen no link with GBS, Although one review gives an incidence of about one case per million vaccinations, a large study in China, reported in The New England Journal of Medicine covering close to 100 million doses of H1N1 flu vaccine found only eleven cases of Guillain-Barre 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...
, actually lower than the normal rate of the disease in China, and no other notable side effects.
Pregnant women and children
A 2009 review of the use of influenza vaccines in pregnant women stated that influenza infections posed a major risk during pregnancy and that multiple studies had shown that the inactivated vaccine was safe in pregnant women, concluding that this vaccine "can be safely and effectively administered during any trimester of pregnancy" and that high levels of immunization would avert a "a significant number of deaths". A 2004 review of the safety of influenza vaccines in children stated that the live vaccine had been shown to be safe but that it might trigger wheezing in some children with asthma; less data for the trivalent inactivated vaccine was available, but no serious symptoms had been seen in clinical trials.Squalene
Newsweek states that "wild rumours" about the swine flu vaccine are being spread through e-mails, it writes that "The claims are nearly pure bunk, with only trace amounts of fact." These rumours generally make unfounded claims that the vaccine is dangerous and they may also promote conspiracy theoriesConspiracy theory
A conspiracy theory explains an event as being the result of an alleged plot by a covert group or organization or, more broadly, the idea that important political, social or economic events are the products of secret plots that are largely unknown to the general public.-Usage:The term "conspiracy...
. For example, Newsweek states that some chain e-mails make false claims about squalene
Squalene
Squalene is a natural organic compound originally obtained for commercial purposes primarily from shark liver oil, though plant sources are used as well, including amaranth seed, rice bran, wheat germ, and olives. All plants and animals produce squalene, including humans...
(shark liver oil) in vaccines. The New York Times also notes that anti-vaccine groups have spread "dire warnings" about formulations of the vaccine that contain squalene as an 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...
. An adjuvant is a substance that boosts the body's immune response, thereby stretching the supply of the vaccine and helping immunize elderly people with a weak immune system. Squalene is a normal part of the human body, made in the liver and circulating in the blood, and is also found in many foods, such as egg
Egg (food)
Eggs are laid by females of many different species, including birds, reptiles, amphibians, and fish, and have probably been eaten by mankind for millennia. Bird and reptile eggs consist of a protective eggshell, albumen , and vitellus , contained within various thin membranes...
s and olive oil
Olive oil
Olive oil is an oil obtained from the olive , a traditional tree crop of the Mediterranean Basin. It is commonly used in cooking, cosmetics, pharmaceuticals, and soaps and as a fuel for traditional oil lamps...
. None of the formulations of vaccine used in the US contain squalene, or any other adjuvant. However, some European and Canadian formulations do contain 25 μg of squalene per dose, which is roughly the amount found in a drop of olive oil. Some animal experiments have suggested that squalene might be linked to autoimmune disorders. although others suggest squalene might protect people against cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
.
Squalene-based adjuvants have been used in 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...
an influenza vaccines since 1997, with about 22 million doses administered over the past twelve years. The WHO states that no severe side effects have been associated with these vaccines, although they can produce mild inflammation at the site of injection. The safety of squalene-containing influenza vaccines have also been tested in two separate clinical trials, one with healthy non-elderly people, and one with elderly people, in both trials the vaccine was safe and well-tolerated, with only weak side-effects such as mild pain at the injection site. A 2009 meta-analysis
Meta-analysis
In statistics, a meta-analysis combines the results of several studies that address a set of related research hypotheses. In its simplest form, this is normally by identification of a common measure of effect size, for which a weighted average might be the output of a meta-analyses. Here the...
brought together data from 64 clinical trials of influenza vaccines with the squalene-containing adjuvant MF59 and compared them to the effects of vaccines with no adjuvant. The analysis reported that the adjuvanted vaccines were associated with slightly lower risks of chronic diseases, but that neither type of vaccines altered the normal rate of autoimmune diseases; the authors concluded that their data "supports the good safety profile associated with MF59-adjuvanted influenza vaccines and suggests there may be a clinical benefit over non-MF59-containing vaccines". A 2004 review of the effects of adjuvants on mice and humans concluded that "despite numerous case reports on vaccination induced autoimmunity, most epidemiological studies failed to confirm the association and the risk appears to be extremely low or non-existent", although the authors noted that the possibility that adjuvants might cause damaging immune reactions in a few susceptible people has not been completely ruled out. A 2009 review of oil-based adjuvants in influenza vaccines stated that this type of adjuvant "neither stimulates antibodies against squalene oil naturally produced by the humans body nor enhances titers of preexisting antibodies to squalene" and that these formulations did not raise any safety concerns.
A paper published in 2000 suggested that squalene might have caused of Gulf War syndrome
Gulf War syndrome
Gulf War syndrome or Gulf War illness describes a medical condition that affected veterans and civilians who were near conflicts during or downwind of chemical weapons depot demolition, after the 1991 Gulf War. A wide range of acute and chronic symptoms have included fatigue, musculoskeletal...
by producing anti-squalene antibodies, although other scientists stated that it was uncertain if the methods used were actually capable of detecting these antibodies. A 2009 U.S. Department of Defense study comparing healthy Navy personnel to those suffering from Gulf War syndrome was published in the journal Vaccine, this used a validated test for these antibodies and found no link between the presence of the antibodies and illness, with about half of both groups having these antibodies and no correlation between symptoms and antibodies. Furthermore, none of the vaccines given to US troops during the Gulf war actually contained any squalene adjuvants.
Thiomersal
Multi-dose versions of the vaccine contain the preservative thiomersalThiomersal
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), a mercury
Mercury (element)
Mercury is a chemical element with the symbol Hg and atomic number 80. It is also known as quicksilver or hydrargyrum...
compound that prevents contamination when the vial is used repeatedly. Single-dose versions and the live vaccine do not contain this preservative. In the U.S., one dose from a multi-dose vial contains approximately 25 micrograms of mercury, a bit less than a typical tuna fish sandwich
Tuna fish sandwich
A tuna fish sandwich, a tuna salad sandwich, or tuna sandwich, is a type of sandwich usually made with tuna salad and includes ingredients such as mayonnaise and celery...
. In Canada, different variants contain five and 50 micrograms of thimerosal per dose. The use of thiomersal has been controversial
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...
, with claims that it can cause autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
and other developmental disorder
Developmental disorder
Developmental disorders occur at some stage in a child's development, often retarding the development. These may include,psychological or physical disorders. The disorder is an impairment in the normal development of motor or cognitive skills that are developed before age 18 in which they are...
s. The U.S. Institute of Medicine
Institute of Medicine
The Institute of Medicine is a not-for-profit, non-governmental American organization founded in 1970, under the congressional charter of the National Academy of Sciences...
examined these claims and concluded in 2004 that the evidence did not support any link between vaccines and autism. Other reviews came to similar conclusions, with a 2006 review in the Canadian Journal of Neurological Sciences stating that there is no convincing evidence to support the claim that thimerosal has a causal role in autism, and a 2009 review in the journal Clinical Infectious Diseases
Clinical Infectious Diseases
Clinical Infectious Diseases in a peer-reviewed medical journal published by Oxford University Press covering research on the pathogenesis, clinical investigation, medical microbiology, diagnosis, immune mechanisms, and treatment of diseases caused by infectious agents...
stating that claims that mercury can cause autism are "biologically implausible". The U.K. National Health Service
National Health Service
The National Health Service is the shared name of three of the four publicly funded healthcare systems in the United Kingdom. They provide a comprehensive range of health services, the vast majority of which are free at the point of use to residents of the United Kingdom...
stated in 2003 that "There is no evidence of long-term adverse effects due to the exposure levels of thiomersal in vaccines." 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...
concluded that there is "no evidence of toxicity in infants, children or adults exposed to thiomersal in vaccines". Indeed, in 2008 a review noted that even though thiomersal was removed from all US childhood vaccines in 2001, this has not changed the number of autism diagnoses, which are still increasing.
Dystonia
According to the CDC, there is no evidence either for or against dystoniaDystonia
Dystonia is a neurological movement disorder, in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures. The disorder may be hereditary or caused by other factors such as birth-related or other physical trauma, infection, poisoning or reaction to...
being caused by the vaccinations. Dystonia is extremely rare. Due to the very low numbers of cases, dystonia is poorly-understood. There were only five cases noted that might have been associated with influenza vaccinations over a span of eighteen years. In one recent case, a woman noted flu-like symptoms, followed by difficulties with movement and speech starting ten days after a seasonal influenza vaccination. However the Dystonia Medical Research Foundation stated that it is unlikely that the symptoms in this case were actually dystonia and stated that there has "never been a validated case of dystonia resulting from a flu shot".
Children Vaccine Recall
On December 15, 2009, One of the five manufacturers supplying the H1N1 vaccine to the United States recalled thousands of doses because they were not as potent as expected. The French manufacturer Sanofi PasteurSanofi pasteur
Sanofi Pasteur is the vaccines division of sanofi-aventis Group. It is the largest company in the world devoted entirely to vaccines.- History :...
voluntarily recalled about 800,000 doses of vaccine meant for children between the ages of six months and 35 months. The company and 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) emphasized that the recall was not prompted by safety concerns, and that even though the vaccine is not quite as potent as it is supposed to be, children who received it do not need to be immunized again. The CDC emphasized that there is no danger for any child who received the recalled vaccine. When asked what parents should do, CDC spokesman Tom Skinner said, "absolutely nothing." He said if children receive this vaccine, they will be fine.
Centers for Disease Control and Prevention
The American Centers for Disease Control and PreventionCenters 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...
issued the following recommendations on who should be vaccinated (order is not in priority):
In addition, the CDC recommends
National Health Service
Britain's National Health ServiceNational Health Service
The National Health Service is the shared name of three of the four publicly funded healthcare systems in the United Kingdom. They provide a comprehensive range of health services, the vast majority of which are free at the point of use to residents of the United Kingdom...
policy is to provide vaccine in this order of priority:
This excludes the large majority of individuals aged six months to 24 years, a group for which the CDC recommends vaccination.
The NHS notes that:
- Healthy people over 65 years of age seem to have some natural immunity.
- Children, while disproportionately affected, tend to make full recoveries.
- The vaccine is ineffective in young infants.
The United Kingdom began its administration program October 21, 2009. UK Soldiers serving in Afghanistan
Afghanistan
Afghanistan , officially the Islamic Republic of Afghanistan, is a landlocked country located in the centre of Asia, forming South Asia, Central Asia and the Middle East. With a population of about 29 million, it has an area of , making it the 42nd most populous and 41st largest nation in the world...
will also be offered vaccination.
Surplus vaccine
By April 2010, it was apparent that most of the vaccine was not needed. The US government had bought 229 million doses of H1N1 vaccines of which 91 million doses were used; of the surplus, some of it was stored in bulk, some of it was sent to developing countries and 71 million doses will be destroyed. The World Health OrganizationWorld 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...
is planning to examine if it overreacted to the H1N1 outbreak.
Political issues
General political issues, not restricted to the 2009 outbreak, arose regarding the distribution of vaccine. In many countries supplies are controlled by national or local governments, and the question of how the vaccine will be allocated should there be an insufficient supply for everyone is critical, and will likely depend on the patterns of any pandemic, and the age groups most at risk for serious complications, including death. In the case of a lethal pandemic people will be demanding access to the vaccine and the major problem will be making it available to those who need it.While it has been suggested that compulsory vaccination may be needed to control a pandemic, many countries do not have a legal framework that would allow this. The only populations easily compelled to accept vaccination are military personnel (who can be given routine vaccinations as part of their service obligations), health care personnel (who can be required to be vaccinated to protect patients), and school children, who (under United States constitutional law) could be required to be vaccinated as a condition of attending school.
In August 2010, the Daily Mail
Daily Mail
The Daily Mail is a British daily middle-market tabloid newspaper owned by the Daily Mail and General Trust. First published in 1896 by Lord Northcliffe, it is the United Kingdom's second biggest-selling daily newspaper after The Sun. Its sister paper The Mail on Sunday was launched in 1982...
printed an article that stated that "a third of the experts advising the World Health Organisation about the swine flu pandemic had ties to drugs firms" and that of the 20 members of the Scientific Advisory Group for Emergencies, which advised the British Government on swine flu, 11 had done work for the pharmaceutical industry or were linked to it through their universities. A spokesman for the WHO is stated as having "denied that the experts' work gave rise to a conflict of interest".
External links
- Swine flu vaccination according to professionals (Faculty Of Medicine)
- "2009 H1N1 Vaccine Doses Allocated, Ordered, and Shipped by Project Area" (CDC)
- Vaccines for pandemic (H1N1) 2009. World Health OrganizationWorld Health OrganizationThe 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...
(WHO). - Vaccine against 2009 H1N1 Influenza Virus. Centers for Disease Control and PreventionCenters for Disease Control and PreventionThe 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). - 2009 influenza A (H1N1) pandemic. European Centre for Disease Prevention and ControlEuropean Centre for Disease Prevention and ControlThe European Centre for Disease Prevention and Control is an independent agency of the European Union aimed at strengthening Europe's defences against infectious diseases. It was established in 2005 and is located in Solna, Sweden....
(ECDC). - Summaries of the pandemic. European Centre for Disease Prevention and ControlEuropean Centre for Disease Prevention and ControlThe European Centre for Disease Prevention and Control is an independent agency of the European Union aimed at strengthening Europe's defences against infectious diseases. It was established in 2005 and is located in Solna, Sweden....
(ECDC).