Polio vaccine

Polio vaccine

Overview
Two polio 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...

s
are used throughout the world to combat poliomyelitis
Poliomyelitis
Poliomyelitis, often called polio or infantile paralysis, is an acute viral infectious disease spread from person to person, primarily via the fecal-oral route...

 (or polio). The first was developed by Jonas Salk
Jonas Salk
Jonas Edward Salk was an American medical researcher and virologist, best known for his discovery and development of the first safe and effective polio vaccine. He was born in New York City to parents from Ashkenazi Jewish Russian immigrant families...

 and first tested in 1952. Announced to the world by Salk on April 12, 1955, it consists of an injected dose of inactivated (dead) poliovirus
Poliovirus
Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and member of the family of Picornaviridae.Poliovirus is composed of an RNA genome and a protein capsid. The genome is a single-stranded positive-sense RNA genome that is about 7500 nucleotides long. The viral particle is...

. An oral vaccine was developed by Albert Sabin
Albert Sabin
Albert Bruce Sabin was an American medical researcher best known for having developed an oral polio vaccine.-Life:...

 using attenuated
Attenuated virus
An attenuated vaccine is a vaccine created by reducing the virulence of a pathogen, but still keeping it viable . Attenuation takes an infectious agent and alters it so that it becomes harmless or less virulent. These vaccines contrast to those produced by "killing" the virus .-Examples:Examples of...

 poliovirus. Human trials
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...

 of Sabin's vaccine began in 1957 and it was licensed in 1962. Because there is no long term carrier
Asymptomatic carrier
An asymptomatic carrier is a person or other organism that has contracted an infectious disease, but who displays no symptoms. Although unaffected by the disease themselves, carriers can transmit it to others...

 state for poliovirus in immunocompetent individuals, polioviruses have no non-primate reservoir in nature, and survival of the virus in the environment for an extended period of time appears to be remote.
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Encyclopedia
Two polio 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...

s
are used throughout the world to combat poliomyelitis
Poliomyelitis
Poliomyelitis, often called polio or infantile paralysis, is an acute viral infectious disease spread from person to person, primarily via the fecal-oral route...

 (or polio). The first was developed by Jonas Salk
Jonas Salk
Jonas Edward Salk was an American medical researcher and virologist, best known for his discovery and development of the first safe and effective polio vaccine. He was born in New York City to parents from Ashkenazi Jewish Russian immigrant families...

 and first tested in 1952. Announced to the world by Salk on April 12, 1955, it consists of an injected dose of inactivated (dead) poliovirus
Poliovirus
Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and member of the family of Picornaviridae.Poliovirus is composed of an RNA genome and a protein capsid. The genome is a single-stranded positive-sense RNA genome that is about 7500 nucleotides long. The viral particle is...

. An oral vaccine was developed by Albert Sabin
Albert Sabin
Albert Bruce Sabin was an American medical researcher best known for having developed an oral polio vaccine.-Life:...

 using attenuated
Attenuated virus
An attenuated vaccine is a vaccine created by reducing the virulence of a pathogen, but still keeping it viable . Attenuation takes an infectious agent and alters it so that it becomes harmless or less virulent. These vaccines contrast to those produced by "killing" the virus .-Examples:Examples of...

 poliovirus. Human trials
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...

 of Sabin's vaccine began in 1957 and it was licensed in 1962. Because there is no long term carrier
Asymptomatic carrier
An asymptomatic carrier is a person or other organism that has contracted an infectious disease, but who displays no symptoms. Although unaffected by the disease themselves, carriers can transmit it to others...

 state for poliovirus in immunocompetent individuals, polioviruses have no non-primate reservoir in nature, and survival of the virus in the environment for an extended period of time appears to be remote. Therefore, interruption of person to person transmission of the virus by vaccination is the critical step in global polio eradication. The two vaccines have eliminated polio
Poliomyelitis eradication
The global eradication of poliomyelitis is a public health effort to eliminate all cases of poliomyelitis infection around the world. The global effort, begun in 1988 and led by the World Health Organization, UNICEF and The Rotary Foundation, has reduced the number of annual diagnosed cases from...

 from most countries in the world, and reduced the worldwide incidence from an estimated 350,000 cases in 1988 to 1,652 cases in 2007.

Development


In the generic sense, vaccination works by priming 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...

 with an 'immunogen'. Stimulating immune response, via use of an infectious agent, is known as immunization
Immunization
Immunization, or immunisation, is the process by which an individual's immune system becomes fortified against an agent ....

. The development of immunity to polio efficiently blocks person-to-person transmission of wild poliovirus, thereby protecting both individual vaccine recipients and the wider community
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...

.

In 1936, Maurice Brodie, a research assistant at New York University
New York University
New York University is a private, nonsectarian research university based in New York City. NYU's main campus is situated in the Greenwich Village section of Manhattan...

, attempted to produce a formaldehyde
Formaldehyde
Formaldehyde is an organic compound with the formula CH2O. It is the simplest aldehyde, hence its systematic name methanal.Formaldehyde is a colorless gas with a characteristic pungent odor. It is an important precursor to many other chemical compounds, especially for polymers...

-killed polio vaccine from ground-up monkey spinal cord
Spinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...

s. His initial attempts were hampered by the difficulty of obtaining enough virus. Brodie first tested the vaccine on himself and several of his assistants. He then gave the vaccine to three thousand children, many of whom developed allergic reactions, but none developed immunity to polio. Philadelphia pathologist John Kolmer also claimed to have developed a vaccine that same year, but it too produced no immunity and was blamed for causing cases of paralytic polio, nine of them fatal.

A breakthrough came in 1948 when a research group headed by John Enders at the Children's Hospital Boston
Children's Hospital Boston
Children's Hospital Boston is a 396-licensed bed children's hospital in the Longwood Medical and Academic Area of Boston, Massachusetts.At 300 Longwood Avenue, Children's is adjacent both to its teaching affiliate, Harvard Medical School, and to Dana-Farber Cancer Institute...

 successfully cultivated the poliovirus
Poliovirus
Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and member of the family of Picornaviridae.Poliovirus is composed of an RNA genome and a protein capsid. The genome is a single-stranded positive-sense RNA genome that is about 7500 nucleotides long. The viral particle is...

 in human tissue in the laboratory. This group had recently successfully grown mumps in cell culture. In March 1948 Weller was attempting to grow varicella virus in embryonic lung tissue. He had inoculated the planned number of tubes when he noticed that there were a few unused tubes. He retrieved a sample of mouse brain infected with polio virus and added it to the remaining test tubes, on the off chance that the virus might grow. The varicella cultures failed to grow but the polio cultures were successful.

This development greatly facilitated vaccine research and ultimately allowed for the development of vaccines against polio. Enders and his colleagues, Thomas H. Weller and Frederick C. Robbins, were recognized in 1954 for their labors with a Nobel Prize in Physiology or Medicine
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite, in his will...

. Other important advances that led to the development of polio vaccines were: the identification of three poliovirus serotype
Serotype
Serotype or serovar refers to distinct variations within a subspecies of bacteria or viruses. These microorganisms, viruses, or cells are classified together based on their cell surface antigens...

s (Poliovirus type 1 — PV1, or Mahoney; PV2, Lansing; and PV3, Leon); the finding that prior to paralysis, the virus must be present in the blood; and the demonstration that administration of antibodies in the form of gamma-globulin protects against paralytic polio.

In 1952 and 1953, the U.S. experienced an outbreak of 58,000 and 35,000 polio cases, respectively, up from a typical number of some 20,000 a year. Amid this U.S. polio epidemic, millions of dollars were invested in finding and marketing a polio vaccine by commercial interests, including Lederle Laboratories in New York under the direction of H. R. Cox
H. R. Cox
Herald Rea Cox was an American bacteriologist. Born in Terre Haute, Indiana, he graduated from Indiana State Normal School, now Indiana State University, in 1928 before obtaining his doctorate from the Johns Hopkins Bloomberg School of Public Health....

. Also working at Lederle was Polish-born virologist and immunologist Hilary Koprowski
Hilary Koprowski
Hilary Koprowski is a Polish virologist and immunologist, and inventor of the world's first effective live polio vaccine.-Life:...

, who claims to have created the first successful polio vaccine, in 1950. His vaccine, however, being a live attenuated virus taken orally, was still in the research stage and would not be ready for use until five years after Jonas Salk's polio vaccine (a dead injectable vaccine) had reached the market. Koprowski's attenuated vaccine was prepared by successive passages through the brains of Swiss albino mice. By the seventh passage, the vaccine strains could no longer infect nervous tissue or cause paralysis. After one to three further passages on rats, the vaccine was deemed safe for human use. On February 27, 1950, Koprowski's live, attenuated vaccine was tested for the first time on an 8-year-old boy living at Letchworth Village
Letchworth Village
Letchworth Village was a residential institution located in Rockland County, New York, built for the physically and mentally disabled of all ages from the newborn to the elderly...

, an institution for the physically and mentally disabled located in New York. After the child suffered no side effects, Koprowski enlarged his experiment to include 19 other children.

The development of two polio vaccines led to the first modern mass inoculation
Inoculation
Inoculation is the placement of something that will grow or reproduce, and is most commonly used in respect of the introduction of a serum, vaccine, or antigenic substance into the body of a human or animal, especially to produce or boost immunity to a specific disease...

s. The last cases of paralytic poliomyelitis caused by endemic transmission of wild virus in the United States occurred in 1979, with an outbreak among the Amish
Amish
The Amish , sometimes referred to as Amish Mennonites, are a group of Christian church fellowships that form a subgroup of the Mennonite churches...

 in several Midwest states. A global effort to eradicate polio, led by 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...

, UNICEF, and The Rotary Foundation, began in 1988 and has relied largely on the oral polio vaccine developed by Albert Sabin
Albert Sabin
Albert Bruce Sabin was an American medical researcher best known for having developed an oral polio vaccine.-Life:...

. The disease was entirely eradicated in the Americas
Americas
The Americas, or America , are lands in the Western hemisphere, also known as the New World. In English, the plural form the Americas is often used to refer to the landmasses of North America and South America with their associated islands and regions, while the singular form America is primarily...

 by 1994. Polio was officially eradicated in 36 Western Pacific countries, including China and Australia in 2000. 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...

 was declared polio-free in 2002. As of 2008, polio remains endemic
Endemic (epidemiology)
In epidemiology, an infection is said to be endemic in a population when that infection is maintained in the population without the need for external inputs. For example, chickenpox is endemic in the UK, but malaria is not...

 in only four countries: Nigeria
Nigeria
Nigeria , officially the Federal Republic of Nigeria, is a federal constitutional republic comprising 36 states and its Federal Capital Territory, Abuja. The country is located in West Africa and shares land borders with the Republic of Benin in the west, Chad and Cameroon in the east, and Niger in...

, India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...

, Pakistan
Pakistan
Pakistan , officially the Islamic Republic of Pakistan is a sovereign state in South Asia. It has a coastline along the Arabian Sea and the Gulf of Oman in the south and is bordered by Afghanistan and Iran in the west, India in the east and China in the far northeast. In the north, Tajikistan...

, and 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...

. Although poliovirus transmission has been interrupted in much of the world, transmission of wild poliovirus does continue and creates an ongoing risk for the importation of wild poliovirus into previously polio-free regions. If importations of poliovirus occurs, outbreaks of poliomyelitis may develop, especially in areas with low vaccination coverage and poor sanitation. As a result, high levels of vaccination coverage must be maintained.

Inactivated vaccine



The first effective polio vaccine was developed in 1952 by Jonas Salk
Jonas Salk
Jonas Edward Salk was an American medical researcher and virologist, best known for his discovery and development of the first safe and effective polio vaccine. He was born in New York City to parents from Ashkenazi Jewish Russian immigrant families...

 at the University of Pittsburgh
University of Pittsburgh
The University of Pittsburgh, commonly referred to as Pitt, is a state-related research university located in Pittsburgh, Pennsylvania, United States. Founded as Pittsburgh Academy in 1787 on what was then the American frontier, Pitt is one of the oldest continuously chartered institutions of...

, but it would require years of testing. To encourage patience, Salk went on CBS radio to report a successful test on a small group of adults and children on March 26, 1953; two days later the results were published in JAMA
Jama
Jama or JAMA may refer to:* Jama Software, a privately held company in Portland, Oregon* Journal of the American Medical Association, an international peer-reviewed general medical journal...

.

The Salk vaccine, or inactivated poliovirus vaccine (IPV), is based on three wild, virulent reference strains, Mahoney (type 1 poliovirus), MEF-1 (type 2 poliovirus), and Saukett (type 3 poliovirus), grown in a type of monkey kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...

 tissue culture (Vero cell line), which are then inactivated with formalin. The injected Salk vaccine confers IgG-mediated immunity in the bloodstream, which prevents polio infection from progressing to viremia
Viremia
Viremia is a medical condition where viruses enter the bloodstream and hence have access to the rest of the body. It is similar to bacteremia, a condition where bacteria enter the bloodstream.- Primary versus Secondary :...

 and protects the motor neurons, thus eliminating the risk of bulbar polio and post-polio syndrome
Post-polio syndrome
Post-polio syndrome is a condition that affects approximately 25–50% of people who have previously contracted poliomyelitis—a viral infection of the nervous system—after the initial infection. Typically the symptoms appear 15–30 years after recovery from the original paralytic attack, at an age of...

.

Beginning February 23, 1954, the vaccine was tested at Arsenal Elementary School and the Watson Home for Children in Pittsburgh, Pennsylvania
Pittsburgh, Pennsylvania
Pittsburgh is the second-largest city in the US Commonwealth of Pennsylvania and the county seat of Allegheny County. Regionally, it anchors the largest urban area of Appalachia and the Ohio River Valley, and nationally, it is the 22nd-largest urban area in the United States...

. Salk's vaccine was then used in a test called the Francis Field Trial, led by Thomas Francis
Thomas Francis, Jr.
Thomas Francis, Jr. was an American physician, virologist, and epidemiologist. Francis was the first person to isolate influenza virus in America, and in 1940 showed that there are other strains of influenza, and took part in the development of influenza vaccines.- Life and achievements :Francis...

; the largest medical experiment in history. The test began with some 4,000 children at Franklin Sherman Elementary School in McLean, Virginia
McLean, Virginia
McLean is an unincorporated community and census-designated place in Fairfax County in Northern Virginia. The community had a total population of 48,115 as of the 2010 census....

, and would eventually involve 1.8 million children, in 44 states from Maine
Maine
Maine is a state in the New England region of the northeastern United States, bordered by the Atlantic Ocean to the east and south, New Hampshire to the west, and the Canadian provinces of Quebec to the northwest and New Brunswick to the northeast. Maine is both the northernmost and easternmost...

 to California
California
California is a state located on the West Coast of the United States. It is by far the most populous U.S. state, and the third-largest by land area...

. By the conclusion of the study, roughly 440,000 received one or more injections of the vaccine, about 210,000 children received a placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...

, consisting of harmless culture media, and 1.2 million children received no vaccination and served as a control group, who would then be observed to see if any contracted polio. The results of the field trial were announced April 12, 1955 (the tenth anniversary of the death of Franklin D. Roosevelt
Franklin D. Roosevelt
Franklin Delano Roosevelt , also known by his initials, FDR, was the 32nd President of the United States and a central figure in world events during the mid-20th century, leading the United States during a time of worldwide economic crisis and world war...

; see Franklin D. Roosevelt's paralytic illness
Franklin D. Roosevelt's paralytic illness
Franklin D. Roosevelt's paralytic illness began in 1921 at age 39, when Roosevelt got a fever after exercising heavily at a vacation in Canada. While his bout with illness was well known during his terms as President of the United States, the extent of his paralysis was kept from public view. After...

). The Salk vaccine had been 60 - 70% effective against PV1 (poliovirus type 1), over 90% effective against PV2 and PV3, and 94% effective against the development of bulbar polio. Soon after Salk's vaccine was licensed in 1955 children's vaccination campaigns were launched. In the U.S, following a mass immunization campaign promoted by the March of Dimes
March of Dimes
The March of Dimes Foundation is a United States nonprofit organization that works to improve the health of mothers and babies.-Organization:...

, the annual number of polio cases fell from 35,000 in 1953 to 5,600 by 1957. By 1961 only 161 cases were recorded in the United States.


An enhanced-potency
Potency (pharmacology)
In the field of pharmacology, potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. A highly potent drug evokes a larger response at low concentrations, while a drug of lower potency evokes a small response at low concentrations...

 IPV was licensed in the United States in November 1987, and is currently the vaccine of choice in the United States. The first dose of polio vaccine is given shortly after birth, usually between 1–2 months of age, a second dose is given at 4 months of age. The timing of the third dose depends on the vaccine formulation but should be given between 6–18 months of age. A booster vaccination is given at 4 to 6 years of age, for a total of four doses at or before school entry. In some countries, a fifth vaccination is given during adolescence
Adolescence
Adolescence is a transitional stage of physical and mental human development generally occurring between puberty and legal adulthood , but largely characterized as beginning and ending with the teenage stage...

. Routine vaccination of adults (18 years of age and older) in developed countries is neither necessary nor recommended because most adults are already immune and have a very small risk of exposure to wild poliovirus in their home countries.

In 2002, a pentavalent (5-component) combination vaccine (called Pediarix) containing IPV was approved for use in the United States. The vaccine also contains combined diphtheria
Diphtheria
Diphtheria is an upper respiratory tract illness caused by Corynebacterium diphtheriae, a facultative anaerobic, Gram-positive bacterium. It is characterized by sore throat, low fever, and an adherent membrane on the tonsils, pharynx, and/or nasal cavity...

, tetanus
Tetanus
Tetanus is a medical condition characterized by a prolonged contraction of skeletal muscle fibers. The primary symptoms are caused by tetanospasmin, a neurotoxin produced by the Gram-positive, rod-shaped, obligate anaerobic bacterium Clostridium tetani...

, and acellular pertussis
Pertussis
Pertussis, also known as whooping cough , is a highly contagious bacterial disease caused by Bordetella pertussis. Symptoms are initially mild, and then develop into severe coughing fits, which produce the namesake high-pitched "whoop" sound in infected babies and children when they inhale air...

 vaccines (DTaP) and a pediatric dose of hepatitis B vaccine. In the UK, IPV is combined with tetanus, diphtheria, pertussis and Haemophilus influenzae
Haemophilus influenzae
Haemophilus influenzae, formerly called Pfeiffer's bacillus or Bacillus influenzae, Gram-negative, rod-shaped bacterium first described in 1892 by Richard Pfeiffer during an influenza pandemic. A member of the Pasteurellaceae family, it is generally aerobic, but can grow as a facultative anaerobe. H...

type b vaccines. When the current formulation of IPV is used, 90% or more of individuals develop protective antibody to all three serotype
Serotype
Serotype or serovar refers to distinct variations within a subspecies of bacteria or viruses. These microorganisms, viruses, or cells are classified together based on their cell surface antigens...

s of poliovirus after two doses of inactivated polio vaccine (IPV), and at least 99% are immune to poliovirus following three doses. The duration of immunity induced by IPV is not known with certainty, although a complete series is thought to provide protection for many years.

Oral vaccine


Oral polio vaccine (OPV) is a live-attenuated vaccine, produced by the passage of the virus through non-human cells at a sub-physiological temperature, which produces spontaneous mutations in the viral genome. Oral polio vaccines were developed by several groups, one of which was led by Albert Sabin
Albert Sabin
Albert Bruce Sabin was an American medical researcher best known for having developed an oral polio vaccine.-Life:...

. Other groups, led by Hilary Koprowski
Hilary Koprowski
Hilary Koprowski is a Polish virologist and immunologist, and inventor of the world's first effective live polio vaccine.-Life:...

 and H.R. Cox
H. R. Cox
Herald Rea Cox was an American bacteriologist. Born in Terre Haute, Indiana, he graduated from Indiana State Normal School, now Indiana State University, in 1928 before obtaining his doctorate from the Johns Hopkins Bloomberg School of Public Health....

, developed their own attenuated vaccine strains. In 1958, 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...

 created a special committee on live polio vaccines. The various vaccines were carefully evaluated for their ability to induce immunity to polio, while retaining a low incidence of neuropathogenicity in monkeys. Based on these results, the Sabin strains were chosen for worldwide distribution.

There are 57 nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...

 substitutions which distinguish the attenuated Sabin 1 strain from its virulent parent (the Mahoney serotype), two nucleotide substitutions attenuate the Sabin 2 strain, and 10 substitutions are involved in attenuating the Sabin 3 strain. The primary attenuating factor common to all three Sabin vaccines is a mutation located in the virus's internal ribosome entry site
Internal ribosome entry site
An internal ribosome entry site, abbreviated IRES, is a nucleotide sequence that allows for translation initiation in the middle of a messenger RNA sequence as part of the greater process of protein synthesis...

 (IRES) which alters stem-loop
Stem-loop
Stem-loop intramolecular base pairing is a pattern that can occur in single-stranded DNA or, more commonly, in RNA. The structure is also known as a hairpin or hairpin loop. It occurs when two regions of the same strand, usually complementary in nucleotide sequence when read in opposite directions,...

 structures, and reduces the ability of poliovirus to translate its RNA template within the host cell. The attenuated poliovirus in the Sabin vaccine replicates very efficiently in the gut, the primary site of infection and replication, but is unable to replicate efficiently within nervous system
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...

 tissue. OPV also proved to be superior in administration, eliminating the need for sterile syringes and making the vaccine more suitable for mass vaccination campaigns. OPV also provided longer lasting immunity
Immunity (medical)
Immunity is a biological term that describes a state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion. Immunity involves both specific and non-specific components. The non-specific components act either as barriers or as eliminators of wide...

 than the Salk vaccine.

In 1961, type 1 and 2 monovalent oral poliovirus vaccine (MOPV) was licensed, and in 1962, type 3 MOPV was licensed. In 1963, trivalent OPV (TOPV) was licensed, and became the vaccine of choice in the United States and most other countries of the world, largely replacing the inactivated polio vaccine. A second wave of mass immunizations led to a further dramatic decline in the number of polio cases. Between 1962 and 1965 about 100 million Americans (roughly 56% of the population at that time) received the Sabin vaccine. The result was a substantial reduction in the number of poliomyelitis cases, even from the much reduced levels following the introduction of the Salk vaccine.

OPV is usually provided in vials containing 10-20 doses of vaccine. A single dose of oral polio vaccine (usually two drops) contains 1,000,000 infectious units of Sabin 1 (effective against PV1), 100,000 infectious units of the Sabin 2 strain, and 600,000 infectious units of Sabin 3. The vaccine contains small traces of antibiotics— neomycin
Neomycin
Neomycin is an aminoglycoside antibiotic that is found in many topical medications such as creams, ointments, and eyedrops. The discovery of Neomycin dates back to 1949. It was discovered in the lab of Selman Waksman, who was later awarded the Nobel Prize in Physiology and medicine in 1951...

 and streptomycin
Streptomycin
Streptomycin is an antibiotic drug, the first of a class of drugs called aminoglycosides to be discovered, and was the first antibiotic remedy for tuberculosis. It is derived from the actinobacterium Streptomyces griseus. Streptomycin is a bactericidal antibiotic. Streptomycin cannot be given...

—but does not contain preservative
Preservative
A preservative is a naturally occurring or synthetically produced substance that is added to products such as foods, pharmaceuticals, paints, biological samples, wood, etc. to prevent decomposition by microbial growth or by undesirable chemical changes....

s. One dose of OPV produces immunity to all three poliovirus serotypes in approximately 50% of recipients. Three doses of live-attenuated OPV produce protective antibody to all three poliovirus types in more than 95% of recipients. OPV produces excellent immunity in the intestine
Intestine
In human anatomy, the intestine is the segment of the alimentary canal extending from the pyloric sphincter of the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine...

, the primary site of wild poliovirus entry, which helps prevent infection with wild virus in areas where the virus is endemic
Endemic (epidemiology)
In epidemiology, an infection is said to be endemic in a population when that infection is maintained in the population without the need for external inputs. For example, chickenpox is endemic in the UK, but malaria is not...

. The live virus used in the vaccine is shed in the stool and can be spread to others within a community, resulting in protection against poliomyelitis even in individuals who have not been directly vaccinated. IPV produces less gastrointestinal immunity than does OPV, and primarily acts by preventing the virus from entering the nervous system. In regions without wild poliovirus, inactivated polio vaccine is the vaccine of choice. In regions with higher incidence of polio, and thus a different relative risk between efficacy and reversion of the vaccine to a virulent form, live vaccine is still used. The live virus also has stringent requirements for transport and storage, which are a problem in some hot or remote areas. As with other live-virus vaccines, immunity initiated by OPV is probably lifelong.

Iatrogenic (vaccine-induced) polio


A major concern about the oral polio vaccine (OPV) is its known ability to revert to a form that can achieve neurological infection and cause paralysis. Clinical disease, including paralysis, caused by vaccine-derived poliovirus (VDPV) is indistinguishable from that caused by wild polioviruses. This is believed to be a rare event, but outbreaks of vaccine-associated paralytic poliomyelitis (VAPP) have been reported, and tend to occur in areas of low coverage by OPV, presumably because the OPV is itself protective against the related outbreak strain.


As the incidence of wild polio diminishes, nations transition from use of the oral vaccine back to the injected vaccine because the direct risk of iatrogenic polio (VAPP) due to OPV outweighs the indirect benefit of immunization via subclinical transmission of OPV. When IPV is used, reversion is not possible but there remains a small risk of clinical infection upon exposure to reverted OPV or wild polio virus. Following the widespread use of polio vaccines in the mid-1950s, the incidence of poliomyelitis declined rapidly in many industrialized countries. The use of OPV was discontinued in the United States in 2000 and in 2004 in the UK, but it continues to be used around the globe.

The rate of vaccine-associated paralytic poliomyelitis (VAPP) varies by region but is generally about 1 case per 750,000 vaccine recipients. VAPP is more likely to occur in adults than in children. In immunodeficient children, the risk of VAPP is almost 7,000 times higher, particularly for persons with B-lymphocyte disorders (e.g., agammaglobulinemia and hypogammaglobulinemia
Hypogammaglobulinemia
Hypogammaglobulinemia is a type of immune disorder characterized by a reduction in all types of gamma globulins.Hypogammaglobulinemia is a characteristic of common variable immunodeficiency.-Terminology:...

), which reduce the synthesis of protective antibodies. 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...

 considers the benefits of vaccination to far outweigh the risk of vaccine derived polio. Outbreaks of vaccine derived polio have been stopped by multiple rounds of high-quality vaccination, in order to immunize the entire population.

Outbreaks of VAPP occurred independently in Belarus
Belarus
Belarus , officially the Republic of Belarus, is a landlocked country in Eastern Europe, bordered clockwise by Russia to the northeast, Ukraine to the south, Poland to the west, and Lithuania and Latvia to the northwest. Its capital is Minsk; other major cities include Brest, Grodno , Gomel ,...

 (1965–66), 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...

 (1966–68), Egypt
Egypt
Egypt , officially the Arab Republic of Egypt, Arabic: , is a country mainly in North Africa, with the Sinai Peninsula forming a land bridge in Southwest Asia. Egypt is thus a transcontinental country, and a major power in Africa, the Mediterranean Basin, the Middle East and the Muslim world...

 (1983–1993), Hispaniola
Hispaniola
Hispaniola is a major island in the Caribbean, containing the two sovereign states of the Dominican Republic and Haiti. The island is located between the islands of Cuba to the west and Puerto Rico to the east, within the hurricane belt...

 (2000–2001), Philippines
Philippines
The Philippines , officially known as the Republic of the Philippines , is a country in Southeast Asia in the western Pacific Ocean. To its north across the Luzon Strait lies Taiwan. West across the South China Sea sits Vietnam...

 (2001), Madagascar
Madagascar
The Republic of Madagascar is an island country located in the Indian Ocean off the southeastern coast of Africa...

 (2001–2002), and in Haiti
Haiti
Haiti , officially the Republic of Haiti , is a Caribbean country. It occupies the western, smaller portion of the island of Hispaniola, in the Greater Antillean archipelago, which it shares with the Dominican Republic. Ayiti was the indigenous Taíno or Amerindian name for the island...

 (2002), where political strife and poverty have interfered with vaccination efforts. In 2006 an outbreak of vaccine-derived poliovirus occurred in 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...

. Cases have been reported from 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...

 (2005–2006), Myanmar
Myanmar
Burma , officially the Republic of the Union of Myanmar , is a country in Southeast Asia. Burma is bordered by China on the northeast, Laos on the east, Thailand on the southeast, Bangladesh on the west, India on the northwest, the Bay of Bengal to the southwest, and the Andaman Sea on the south....

 (2006–2007), Iran (1995, 2005–2007), Syria, Kuwait and Egypt. Since 2005, The World Health Organization has been tracking vaccine-caused polio in northern Nigeria caused by a mutation in live oral polio vaccines.

Contamination concerns


In 1960, it was determined that the rhesus monkey kidney cells used to prepare the poliovirus vaccines were infected with the SV40
SV40
SV40 is an abbreviation for Simian vacuolating virus 40 or Simian virus 40, a polyomavirus that is found in both monkeys and humans...

 virus (Simian Virus-40). SV40 was also discovered in 1960 and is a naturally occurring 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...

 that infects monkeys. In 1961, SV40 was found to cause tumors in rodent
Rodent
Rodentia is an order of mammals also known as rodents, characterised by two continuously growing incisors in the upper and lower jaws which must be kept short by gnawing....

s. More recently, the virus was found in certain forms of 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...

 in humans, for instance brain
Brain tumor
A brain tumor is an intracranial solid neoplasm, a tumor within the brain or the central spinal canal.Brain tumors include all tumors inside the cranium or in the central spinal canal...

 and bone tumor
Bone tumor
A bone tumor refers to a neoplastic growth of tissue in bone. Abnormal growths found in the bone can be either benign or malignant .-Classification:...

s, pleural and peritoneal mesothelioma, and some types of non-Hodgkin's lymphoma. However, it has not been determined that SV40 causes these cancers.

SV40 was found to be present in stocks of the injected form of the polio vaccine (IPV) in use between 1955 to 1963. It is not found in the OPV form. Over 98 million Americans received one or more doses of polio vaccine between 1955 to 1963 when a proportion of vaccine was contaminated with SV40; it has been estimated that 10–30 million Americans may have received a dose of vaccine contaminated with SV40. Later analysis suggested that vaccines produced by the former Soviet bloc countries until 1980, and used in the USSR, 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...

, 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 several 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...

n countries, may have been contaminated; meaning hundreds of millions more may have been exposed to SV40.

In 1998, the National Cancer Institute
National Cancer Institute
The National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...

 undertook a large study, using cancer case information from the Institutes SEER database. The published findings from the study revealed that there was no increased incidence of cancer in persons who may have received vaccine containing SV40. Another large study in Sweden examined cancer rates of 700,000 individuals who had received potentially contaminated polio vaccine as late as 1957; the study again revealed no increased cancer incidence between persons who received polio vaccines containing SV40 and those who did not. The question of whether SV40 causes cancer in humans remains controversial however, and the development of improved assays for detection of SV40 in human tissues will be needed to resolve the controversy.

During the race to develop an oral polio vaccine several large scale human trials were undertaken. By 1958, the National Institutes of Health had determined that OPV produced using the Sabin strains were the safest. Between 1957 and 1960, however, Hilary Koprowski continued to administer his vaccine around the world. In Africa, the vaccines were administered to roughly one million people in the Belgian territories, now the Democratic Republic of the Congo
Democratic Republic of the Congo
The Democratic Republic of the Congo is a state located in Central Africa. It is the second largest country in Africa by area and the eleventh largest in the world...

, Rwanda
Rwanda
Rwanda or , officially the Republic of Rwanda , is a country in central and eastern Africa with a population of approximately 11.4 million . Rwanda is located a few degrees south of the Equator, and is bordered by Uganda, Tanzania, Burundi and the Democratic Republic of the Congo...

 and Burundi
Burundi
Burundi , officially the Republic of Burundi , is a landlocked country in the Great Lakes region of Eastern Africa bordered by Rwanda to the north, Tanzania to the east and south, and the Democratic Republic of the Congo to the west. Its capital is Bujumbura...

. The results of these human trials have been controversial, and accusations in the 1990s
OPV AIDS hypothesis
The oral polio vaccine AIDS hypothesis argues that the AIDS pandemic originated from live polio vaccines prepared in chimpanzee tissue cultures and then administered to up to one million Africans between 1957 and 1960 in experimental mass vaccination campaigns.Data from molecular biology and...

 arose that the vaccine had created the conditions necessary for transmission of SIV
Simian immunodeficiency virus
Simian immunodeficiency virus , also known as African Green Monkey virus and also as Monkey AIDS is a retrovirus able to infect at least 33 species of African primates...

 from chimpanzee
Chimpanzee
Chimpanzee, sometimes colloquially chimp, is the common name for the two extant species of ape in the genus Pan. The Congo River forms the boundary between the native habitat of the two species:...

s to humans, causing HIV/AIDS. These hypotheses have, however, been refuted. By 2004, cases of poliomyelitis in Africa had been reduced to just a small number of isolated regions in the western portion of the continent, with sporadic cases elsewhere. However, recent opposition to vaccination campaigns has evolved, often relating to fears that the vaccine might induce sterility
Infertility
Infertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term...

. The disease has since resurged in Nigeria
Nigeria
Nigeria , officially the Federal Republic of Nigeria, is a federal constitutional republic comprising 36 states and its Federal Capital Territory, Abuja. The country is located in West Africa and shares land borders with the Republic of Benin in the west, Chad and Cameroon in the east, and Niger in...

 and in several other African nations, which epidemiologists believe is due to refusals by certain local populations to allow their children to receive the polio vaccine.

External links

  • History of Vaccines Website – History of Polio History of Vaccines, a project of the College of Physicians of Philadelphia
  • CGDev.org - 'Vaccines for Development', Center for Global Development
    Center for Global Development
    The Center for Global Development is a non-profit think tank based in Washington, D.C. that focuses on international development. It was founded in November 2001 by former senior U.S. official Edward W. Scott, director of the Peterson Institute for International Economics, C. Fred Bergsten, and...

  • PBS.org - 'People and Discoveries: Salk Produces Polio Vaccine 1952', PBS
    Public Broadcasting Service
    The Public Broadcasting Service is an American non-profit public broadcasting television network with 354 member TV stations in the United States which hold collective ownership. Its headquarters is in Arlington, Virginia....

  • Documents regarding Jonas Salk and the Salk Polio Vaccine, Dwight D. Eisenhower Presidential Library
  • Conquering Polio, Smithsonian Magazine, April 2005