[
]
Allergic reaction to the vaccine
Inactivated polio vaccine can cause an allergic reaction in a few people since the vaccine contains trace amounts of antibiotics, streptomycin, polymyxin B, and neomycin. It should not be given to anyone who has an allergic reaction to these medicines. Signs and symptoms of an allergic reaction, which usually appear within minutes or a few hours after receiving the injected vaccine, include breathing difficulties, weakness, hoarseness or wheezing, heart rate fluctuations, skin rash and dizziness.
Vaccine-induced polio
A potential, adverse effect of the OPV is its known ability to recombine to a form that causes neurological infection and paralysis. This genetic reversal of the pathogen to a virulent form takes a considerable time (at least 12 months) and does not affect the person who was originally vaccinated. The vaccine-derived attenuated virus is normally excreted from vaccinated people for a limited period. Thus, in areas with poor sanitation and low vaccination coverage, the spontaneous reversal of the vaccine-derived virus to a virulent form and its spreading in the environment can lead to unvaccinated people becoming infected. Clinical disease, including paralysis, caused by vaccine-derived poliovirus (VDPV) is indistinguishable from that caused by wild polioviruses. Outbreaks of vaccine-associated paralytic poliomyelitis (VAPP), caused by a circulating vaccine-derived poliovirus (cVDPV), 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. With wild polio cases at record lows, 2017 was the first year where more cases of cVDPV were recorded than the wild poliovirus, a trend that is expected to continue.
To combat this, the WHO in 2016, decided to switch from the trivalent polio vaccine to the bivalent polio vaccine. This vaccine no longer contains the type 2 polio virus because it was eradicated in 1999.
Contamination concerns
In 1960, the rhesus monkey kidney cells used to prepare the poliovirus vaccines were determined to be infected with the simian virus-40 (SV40), which was also discovered in 1960 and is a naturally occurring virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsk ...
that infects monkeys. In 1961, SV40 was found to cause tumors in rodent
Rodents (from Latin , 'to gnaw') are mammals of the order Rodentia (), which are characterized by a single pair of continuously growing incisors in each of the upper and lower jaws. About 40% of all mammal species are rodents. They are n ...
s. More recently, the virus was found in certain forms of cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
in humans, for instance brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...
and bone tumor
A bone tumor is an abnormal growth of tissue in bone, traditionally classified as noncancerous (benign) or cancerous (malignant). Cancerous bone tumors usually originate from a cancer in another part of the body such as from lung, breast, thyroi ...
s, pleural and peritoneal
The peritoneum is the serous membrane forming the lining of the abdominal cavity or coelom in amniotes and some invertebrates, such as annelids. It covers most of the intra-abdominal (or coelomic) organs, and is composed of a layer of meso ...
mesothelioma, and some types of non-Hodgkin lymphoma
Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and tirednes ...
. However, SV40 has not been determined to cause these cancers.
SV40 was found to be present in stocks of the injected form of the IPV in use between 1955 and 1963.[ It is not found in the OPV form.][ Over 98 million Americans received one or more doses of polio vaccine between 1955 and 1963 when a proportion of vaccine was contaminated with SV40; an estimated 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
The Soviet Union,. officially the Union of Soviet Socialist Republics. (USSR),. was a transcontinental country that spanned much of Eurasia from 1922 to 1991. A flagship communist state, it was nominally a federal union of fifteen nationa ...
, China, Japan, and several Africa
Africa is the world's second-largest and second-most populous continent, after Asia in both cases. At about 30.3 million km2 (11.7 million square miles) including adjacent islands, it covers 6% of Earth's total surface area ...
n countries, may have been contaminated, meaning hundreds of millions more may have been exposed to SV40.
In 1998, the National Cancer Institute
The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...
undertook a large study, using cancer case information from the institute's SEER database. The published findings from the study revealed 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
Hilary Koprowski (5 December 191611 April 2013) was a Polish virologist and immunologist active in the United States who demonstrated the world's first effective live polio vaccine. He authored or co-authored over 875 scientific papers and co ...
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
The Democratic Republic of the Congo (french: République démocratique du Congo (RDC), colloquially "La RDC" ), informally Congo-Kinshasa, DR Congo, the DRC, the DROC, or the Congo, and formerly and also colloquially Zaire, is a country in ...
, Rwanda, and Burundi). The results of these human trials have been controversial, and unfounded accusations in the 1990s arose that the vaccine had created the conditions necessary for transmission of simian immunodeficiency virus
''Simian immunodeficiency virus'' (''SIV'') is a species of retrovirus that cause persistent infections in at least 45 species of non-human primates. Based on analysis of strains found in four species of monkeys from Bioko Island, which was iso ...
from chimpanzees to humans, causing HIV/AIDS
Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ...
. These hypotheses, however, have been conclusively 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. Recent local opposition to vaccination campaigns have evolved due to lack of adequate information, often relating to fears that the vaccine might induce sterility. The disease has since resurged in Nigeria
Nigeria ( ), , ig, Naìjíríyà, yo, Nàìjíríà, pcm, Naijá , ff, Naajeeriya, kcg, Naijeriya officially the Federal Republic of Nigeria, is a country in West Africa. It is situated between the Sahel to the north and the Gulf o ...
and in several other African nations without necessary information, which epidemiologist
Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and determinants of health and disease conditions in a defined population.
It is a cornerstone of public health, and shapes policy decisions and evidenc ...
s believe is due to refusals by certain local populations to allow their children to receive the polio vaccine.
Manufacture
Inactivated
The Salk vaccine, IPV, is based on three wild, virulent
Virulence is a pathogen's or microorganism's ability to cause damage to a host.
In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ...
reference strains, Mahoney (type 1 poliovirus), MEF-1 (type 2 poliovirus), and Saukett (type 3 poliovirus), grown in a type of monkey kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
tissue culture (Vero cell
Vero cells are a lineage of cells used in cell cultures. The 'Vero' lineage was isolated from kidney epithelial cells extracted from an African green monkey (''Chlorocebus'' sp.; formerly called ''Cercopithecus aethiops'', this group of monkeys ha ...
line), which are then inactivated with formalin
Formaldehyde ( , ) ( systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section F ...
.[ The injected Salk vaccine confers ]IgG
Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG ...
-mediated immunity in the bloodstream, which prevents polio infection from progressing to 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. The name comes from combining the word "virus" wit ...
and protects the motor neurons
A motor neuron (or motoneuron or efferent neuron) is a neuron whose cell body is located in the motor cortex, brainstem or the spinal cord, and whose axon (fiber) projects to the spinal cord or outside of the spinal cord to directly or indirectly ...
, thus eliminating the risk of bulbar polio
Poliomyelitis, commonly shortened to polio, is an infectious disease caused by the poliovirus. Approximately 70% of cases are asymptomatic; mild symptoms which can occur include sore throat and fever; in a proportion of cases more severe sym ...
and post-polio syndrome
Post-polio syndrome (PPS, poliomyelitis sequelae) is a group of latent symptoms of poliomyelitis (polio), occurring at about a 25–40% rate (latest data greater than 80%). These symptoms are caused by the damaging effects of the viral infection ...
.
In the United States, vaccine is administered along with the tetanus
Tetanus, also known as lockjaw, is a bacterial infection caused by ''Clostridium tetani'', and is characterized by muscle spasms. In the most common type, the spasms begin in the jaw and then progress to the rest of the body. Each spasm usually ...
, diphtheria
Diphtheria is an infection caused by the bacterium '' Corynebacterium diphtheriae''. Most infections are asymptomatic or have a mild clinical course, but in some outbreaks more than 10% of those diagnosed with the disease may die. Signs and s ...
, and acellular pertussis
Whooping cough, also known as pertussis or the 100-day cough, is a highly contagious bacterial disease. Initial symptoms are usually similar to those of the common cold with a runny nose, fever, and mild cough, but these are followed by two or t ...
vaccines (DTaP
The DPT vaccine or DTP vaccine is a class of combination vaccines against three infectious diseases in humans: diphtheria, pertussis (whooping cough), and tetanus. The vaccine components include diphtheria and tetanus toxoids and either kille ...
) and a pediatric dose of hepatitis B
Hepatitis B is an infectious disease caused by the '' Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection.
Many people have no symptoms during an initial infection. ...
vaccine.[ In the UK, IPV is combined with tetanus, diphtheria, pertussis, and '']Haemophilus influenzae
''Haemophilus influenzae'' (formerly called Pfeiffer's bacillus or ''Bacillus influenzae'') is a Gram-negative, non-motile, coccobacillary, facultatively anaerobic, capnophilic pathogenic bacterium of the family Pasteurellaceae. The bacter ...
'' type b vaccines.
Attenuated
OPV is an attenuated vaccine
An attenuated vaccine (or a live attenuated vaccine, LAV) is a vaccine created by reducing the virulence of a pathogen, but still keeping it viable (or "live"). Attenuation takes an infectious agent and alters it so that it becomes harmless or less ...
, produced by the passage of the virus through nonhuman 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 Bruce Sabin ( ; August 26, 1906 – March 3, 1993) was a Polish-American medical researcher, best known for developing the oral polio vaccine, which has played a key role in nearly eradicating the disease. In 1969–72, he served as th ...
. Other groups, led by Hilary Koprowski
Hilary Koprowski (5 December 191611 April 2013) was a Polish virologist and immunologist active in the United States who demonstrated the world's first effective live polio vaccine. He authored or co-authored over 875 scientific papers and co ...
and H.R. Cox, developed their own attenuated vaccine strains. In 1958, the National Institutes of Health
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
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. Large-scale clinical trials performed in the Soviet Union in late 1950s to early 1960s by Mikhail Chumakov
Mikhail Petrovich Chumakov (russian: Михаи́л Петро́вич Чумако́в) (November 14, 1909 – June 11, 1993) was a Soviet microbiologist and virologist most famous for conducting pivotal large-scale clinical trials that led to l ...
and his colleagues demonstrated safety and high efficacy of the vaccine. Based on these results, the Sabin strains were chosen for worldwide distribution. Fifty-seven nucleotide
Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecule ...
substitutions 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 An internal ribosome entry site, abbreviated IRES, is an RNA element that allows for translation initiation in a cap-independent manner, as part of the greater process of protein synthesis. In eukaryotic translation, initiation typically occurs at ...
, which alters stem-loop 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
In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes ...
tissue. 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
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention o ...
—neomycin
Neomycin is an aminoglycoside antibiotic that displays bactericidal activity against gram-negative aerobic bacilli and some anaerobic bacilli where resistance has not yet arisen. It is generally not effective against gram-positive bacilli and ...
and streptomycin
Streptomycin is an antibiotic medication used to treat a number of bacterial infections, including tuberculosis, ''Mycobacterium avium'' complex, endocarditis, brucellosis, ''Burkholderia'' infection, plague, tularemia, and rat bite fever. F ...
—but does not contain preservative
A preservative is a substance or a chemical that is added to products such as food products, beverages, pharmaceutical drugs, paints, biological samples, cosmetics, wood, and many other products to prevent decomposition by microbial growth or by ...
s.
History
In a generic sense, vaccination works by priming the immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splint ...
with an 'immunogen
An immunogen is any substance that generates B-cell (humoral/antibody) and/or T-cell (cellular) adaptive immune responses upon exposure to a host organism.
Immunogens that generate antibodies are called antigens ("antibody-generating"). Immunogen ...
'. Stimulating immune response, by use of an infectious agent, is known as immunization
Immunization, or immunisation, is the process by which an individual's immune system becomes fortified against an infectious agent (known as the immunogen).
When this system is exposed to molecules that are foreign to the body, called ''non-se ...
. 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.[
The development of two polio vaccines led to the first modern mass inoculations. 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
The Amish (; pdc, Amisch; german: link=no, Amische), formally the Old Order Amish, are a group of traditionalist Anabaptist Christian church fellowships with Swiss German and Alsatian origins. They are closely related to Mennonite churc ...
in several Midwest states.
1930s
In the 1930s, poliovirus was perceived as especially terrifying, as little was known of how the disease was transmitted or how it could be prevented. This virus was also notable for primarily impacting affluent children, making it a prime target for vaccine development, despite its relatively low mortality and morbidity. Despite this, the community of researchers in the field thus far had largely observed an informal moratorium on any vaccine development as it was perceived to present too high a risk for too little likelihood of success.
This shifted in the early 1930s when American groups took up the challenge: Maurice Brodie
Maurice Brodie (1903–1939) was a British-born American virologist who developed a polio vaccine in 1935.
Early years and education
Brodie was born in Liverpool, England, the son of Samuel Broude and Esther Ginsburg. The family immigrated to Ott ...
led a team from the public health laboratory of the city of New York and Dr. John A. Kolmer collaborated with the Research Institute of Cutaneous Medicine in Philadelphia. The rivalry between these two researchers lent itself to a race-like mentality which, combined with a lack of oversight of medical studies, was reflected in the methodology and outcomes of each of these early vaccine development ventures.
Kolmer's live vaccine
Kolmer began his vaccine development project in 1932 and ultimately focused on producing an attenuated or ''live virus vaccine''. Inspired by the success of vaccines for rabies and yellow fever, he hoped to use a similar process to denature the polio virus. In order to go about attenuating his polio vaccine, he repeatedly passed the virus through monkeys. Using methods of production that were later described as "hair-raisingly amateurish, the therapeutic equivalent of bath-tub gin," Kolmer ground the spinal cords of his infected monkeys and soaked them in a salt solution. He then filtered the solution through mesh, treated it with ricinolate, and refrigerated the product for 14 days to ultimately create what would later be prominently critiqued as a "veritable witches brew".
In keeping with the norms of the time, Kolmer completed a relatively small animal trial with 42 monkeys before proceeding to self experimentation in 1934. He tested his vaccine upon himself, his two children, and his assistant. He gave his vaccine to just 23 more children before declaring it safe and sending it out to doctors and health departments for a larger test of efficacy. By April 1935, he was able to report having tested the vaccine on 100 children without ill effect. Kolmer's first formal presentation of results would not come about until November 1935 where he presented the results of 446 children and adults he had vaccinated with his attenuated vaccine. He also reported that together the Research Institute of Cutaneous Medicine and the Merrell Company of Cincinnati (the manufacturer who held the patent for his ricinoleating process) had distributed 12,000 doses of vaccine to some 700 physicians across the United States and Canada. Kolmer did not describe any monitoring of this experimental vaccination program nor did he provide these physicians with instructions in how to administer the vaccine or how to report side effects. Kolmer dedicated the bulk of his publications thereafter to explaining what he believed to be the cause of the 10+ reported cases of paralytic polio following vaccination, in many cases in towns where no polio outbreak had occurred. Six of these cases had been fatal. Kolmer had no control group but asserted that many more children would have gotten sick.
Brodie's inactivated vaccine
At nearly the same time as Kolmer's project, Maurice Brodie
Maurice Brodie (1903–1939) was a British-born American virologist who developed a polio vaccine in 1935.
Early years and education
Brodie was born in Liverpool, England, the son of Samuel Broude and Esther Ginsburg. The family immigrated to Ott ...
had joined immunologist Dr. William H. Park at the New York City Health Department where they worked together on poliovirus. With the aid of grant funding from the President's Birthday Ball Commission (a predecessor to what would become the March of Dimes), Brodie was able to pursue development of an inactivated or "killed virus" vaccine. Brodie's process also began by grinding the spinal cords of infectious monkeys and then treating the cords with various germicides, ultimately finding a solution of formaldehyde to be the most effective. By 1 June 1934, Brodie was able to publish his first scholarly article describing his successful induction of immunity in three monkeys with inactivated polio virus. Through continued study on an additional 26 monkeys, Brodie ultimately concluded that administration of live virus vaccine tended to result in humoral immunity while administration of killed virus vaccine tended to result in tissue immunity.
Soon after, following a similar protocol to Kolmer, Brodie proceeded with self experimentation upon himself and his co-workers at the NYC Health Department laboratory. Brodie's progress was eagerly covered by popular press as the public hoped for a successful vaccine to become available. Such reporting did not make mention of the 12 children in a New York City Asylum who were subjected to early safety trials. As none of the subjects experienced ill effects, Dr. Park, described by contemporaries as "never one to let grass grow under his feet," declared the vaccine safe. When a severe polio outbreak overwhelmed Kern County
Kern County is a county located in the U.S. state of California. As of the 2020 census, the population was 909,235. Its county seat is Bakersfield.
Kern County comprises the Bakersfield, California, Metropolitan statistical area. The county sp ...
, California
California is a state in the Western United States, located along the Pacific Coast. With nearly 39.2million residents across a total area of approximately , it is the most populous U.S. state and the 3rd largest by area. It is also the m ...
it became the first trial site for the new vaccine on very short notice. Between November 1934 - May 1935, over 1,500 doses of the vaccine were administered in Kern County. While initial results were very promising, insufficient staffing and poor protocol design left Brodie open to criticism when he published the California results in August 1935. Through private physicians, Brodie also conducted a broader field study, including 9,000 children who received the vaccine and 4,500 age- and location-matched controls who did not receive a vaccine. Again, results were promising. Of those who received the vaccine, only a few went on to develop polio. Most had been exposed prior to vaccination and none had received the full series of vaccine doses being studied. Additionally, a polio epidemic in Raleigh
Raleigh (; ) is the capital city of the state of North Carolina and the seat of Wake County in the United States. It is the second-most populous city in North Carolina, after Charlotte. Raleigh is the tenth-most populous city in the Southeas ...
, North Carolina
North Carolina () is a state in the Southeastern region of the United States. The state is the 28th largest and 9th-most populous of the United States. It is bordered by Virginia to the north, the Atlantic Ocean to the east, Georgia and ...
provided an opportunity for the U.S. Public Health Service
The United States Public Health Service (USPHS or PHS) is a collection of agencies of the Department of Health and Human Services concerned with public health, containing nine out of the department's twelve operating divisions. The Assistant ...
to conduct a highly structured trial of the Brodie vaccine using funding from the Birthday Ball Commission.
Academic reception
While their work was ongoing, the larger community of bacteriologist
A bacteriologist is a microbiologist, or similarly trained professional, in bacteriology -- a subdivision of microbiology that studies bacteria, typically pathogenic ones. Bacteriologists are interested in studying and learning about bacteria, ...
s began to raise concerns regarding the safety and efficacy of the new poliovirus vaccines. At this time there was very little oversight of medical studies, and ethical treatment of study participants largely relied upon moral pressure from peer academic scientists. Brodie's inactivated vaccines faced scrutiny from many who felt killed virus vaccines could not be efficacious. While researchers were able to replicate the tissue immunity he had produced in his animal trials, prevailing wisdom was that humoral immunity was essential for an efficacious vaccine. Kolmer directly questioned the killed virus approach in scholarly journals. Kolmer's studies however had raised even more concern with increasing reports of children becoming paralysed following vaccination with his live virus vaccine and notably, with paralysis beginning at the arm rather than the foot in many cases. Both Kolmer and Brodie were called to present their research at the Annual Meeting of the American Public Health Association in Milwaukee
Milwaukee ( ), officially the City of Milwaukee, is both the most populous and most densely populated city in the U.S. state of Wisconsin and the county seat of Milwaukee County. With a population of 577,222 at the 2020 census, Milwaukee ...
WI in October 1935. Additionally, Dr. Thomas M. Rivers was asked to discuss each of the presented papers as a prominent critic of the vaccine development effort. This resulted in the APHA arranging a Symposium on Poliomyelitis to be delivered at the Annual Meeting of their Southern Branch the following month. It was during the discussion at this meeting that Dr. James Leake of the U.S. Public Health Service
The United States Public Health Service (USPHS or PHS) is a collection of agencies of the Department of Health and Human Services concerned with public health, containing nine out of the department's twelve operating divisions. The Assistant ...
stood to immediately present clinical evidence that the Kolmer vaccine had caused several deaths and then allegedly accused Kolmer of being a murderer. As Rivers recalled in his oral history, "All hell broke loose, and it seemed as if everybody was trying to talk at the same time....Jimmy Leake used the strongest language that I have ever heard used at a scientific meeting." In response to the attacks from all sides, Brodie was reported to have stood up and stated, "It looks as though, according to Dr. Rivers, my vaccine is no good, and, according to Dr. Leake, Dr Kolmer's is dangerous." Kolmer simply responded by stating, "Gentlemen, this is one time I wish the floor would open up and swallow me." Ultimately, Kolmer's live vaccine was undoubtedly shown to be dangerous and had already been withdrawn in September 1935 prior to the Milwaukee meeting. While the consensus of the symposium was largely skeptical of the efficacy of Brodie's vaccine, its safety was not in question and the recommendation was for a much larger well-controlled trial. However, when three children became ill with paralytic polio following a dose of the vaccine, the directors of the Warm Springs Foundation in Georgia (acting as the primary funders for the project) requested it be withdrawn in December 1935. Following its withdrawal, the previously observed moratorium on human poliomyelitis vaccine development resumed and there would not be another attempt for nearly 20 years.
While Brodie had arguably made the most progress in the pursuit of a poliovirus vaccine, he suffered the most significant career repercussions due to his status as a less widely known researcher. Modern researchers recognize that Brodie may well have developed an effective polio vaccine, however the basic science and technology of the time was insufficient to understand and utilize this breakthrough. Brodie's work using formalin-inactivated virus would later become the basis for the Salk vaccine, but he would not live to see this success. Brodie was fired from his position within three months of the symposium's publication. While he was able to find another laboratory position, he died of a heart attack only three years later at age 36. By contrast, Park, who was believed in the community to be reaching senility at this point in his older age, was able to retire from his position with honors prior to his death in 1939. Kolmer, already an established and well respected researcher, returned to Temple University
Temple University (Temple or TU) is a public state-related research university in Philadelphia, Pennsylvania. It was founded in 1884 by the Baptist minister Russell Conwell and his congregation Grace Baptist Church of Philadelphia then calle ...
as a professor of medicine. Kolmer had a very productive career, receiving multiple awards, and publishing countless papers, articles, and textbooks up until his retirement in 1957.
1948
A breakthrough came in 1948 when a research group headed by John Enders
John Franklin Enders (February 10, 1897 – September 8, 1985) was an American biomedical scientist and Nobel Laureate. Enders has been called "The Father of Modern Vaccines."
Life and education
Enders was born in West Hartford, Connecticut on F ...
at the Children's Hospital Boston
Boston Children's Hospital formerly known as Children's Hospital Boston until 2012 is a nationally ranked, freestanding acute care children's hospital located in Boston, Massachusetts, adjacent both to its teaching affiliate, Harvard Medical Sch ...
successfully cultivated the poliovirus in human tissue in the laboratory. This group had recently successfully grown mumps in cell culture. In March 1948, Thomas H. 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
The mouse brain refers to the brain of Mus musculus. Various brain atlases exist.
For reasons of reproducibility, genetically characterized, stable strains like C57BL/6 were chosen to produce high-resolution images and databases. Well known onl ...
infected with poliovirus 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 efforts with a Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, accord ...
. Other important advances that led to the development of polio vaccines were: the identification of three poliovirus serotypes (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.
1950–1955
During the early 1950s, polio rates in the U.S. were above 25,000 annually; 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, with deaths in those years numbering 3,200 and 1,400. 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. Also working at Lederle was Polish-born virologist
Virology is the scientific study of biological viruses. It is a subfield of microbiology that focuses on their detection, structure, classification and evolution, their methods of infection and exploitation of host cells for reproduction, thei ...
and immunologist Hilary Koprowski
Hilary Koprowski (5 December 191611 April 2013) was a Polish virologist and immunologist active in the United States who demonstrated the world's first effective live polio vaccine. He authored or co-authored over 875 scientific papers and co ...
of the Wistar Institute in Philadelphia, who tested 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-virus 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 27 February 1950, Koprowski's live, attenuated vaccine was tested for the first time on an 8-year-old boy living at Letchworth Village
Letchworth Village was a residential institution located in Rockland County, New York, in the hamlet of Thiells built for the physically and mentally disabled of all ages, from the newborn to the elderly. Opened in 1911, Letchworth Village at its ...
, an institution for physically and mentally disabled people located in New York. After the child had no side effects, Koprowski enlarged his experiment to include 19 other children.
Jonas Salk
The first effective polio vaccine was developed in 1952 by Jonas Salk
Jonas Edward Salk (; born Jonas Salk; October 28, 1914June 23, 1995) was an American virologist and medical researcher who developed one of the first successful polio vaccines. He was born in New York City and attended the City College of New ...
and a team at the University of Pittsburgh
The University of Pittsburgh (Pitt) is a public state-related research university in Pittsburgh, Pennsylvania. The university is composed of 17 undergraduate and graduate schools and colleges at its urban Pittsburgh campus, home to the univers ...
that included Julius Youngner, Byron Bennett, L. James Lewis, and Lorraine Friedman, which required years of subsequent testing. Salk went on CBS radio to report a successful test on a small group of adults and children on 26 March 1953; two days later, the results were published in ''JAMA
''The Journal of the American Medical Association'' (''JAMA'') is a peer-reviewed medical journal published 48 times a year by the American Medical Association. It publishes original research, reviews, and editorials covering all aspects of biom ...
''. Leone N. Farrell invented a key laboratory technique that enabled the mass production of the vaccine by a team she led in Toronto. Beginning 23 February 1954, the vaccine was tested at Arsenal Elementary School and the Watson Home for Children in Pittsburgh, Pennsylvania
Pittsburgh ( ) is a city in the Commonwealth of Pennsylvania, United States, and the county seat of Allegheny County. It is the most populous city in both Allegheny County and Western Pennsylvania, the second-most populous city in Pennsylva ...
.
Salk's vaccine was then used in a test called the Francis Field Trial, led by Thomas Francis, the largest medical experiment in history at that time. The test began with about 4,000 children at Franklin Sherman Elementary School in McLean, Virginia
McLean ( ) is an unincorporated community and census-designated place (CDP) in Fairfax County in Northern Virginia. McLean is home to many diplomats, military, members of Congress, and high-ranking government officials partially due to its proxi ...
, and eventually involved 1.8 million children, in 44 states from Maine
Maine () is a state in the New England and Northeastern regions of the United States. It borders New Hampshire to the west, the Gulf of Maine to the southeast, and the Canadian provinces of New Brunswick and Quebec to the northeast and ...
to California
California is a state in the Western United States, located along the Pacific Coast. With nearly 39.2million residents across a total area of approximately , it is the most populous U.S. state and the 3rd largest by area. It is also the m ...
. By the conclusion of the study, roughly 440,000 received one or more injections of the vaccine, about 210,000 children received a placebo
A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures.
In general, placebos can af ...
, consisting of harmless culture media
A growth medium or culture medium is a solid, liquid, or semi-solid designed to support the growth of a population of microorganisms or cells via the process of cell proliferation or small plants like the moss ''Physcomitrella patens''. Different ...
, 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 12 April 1955 (the tenth anniversary of the death of President ]Franklin D. Roosevelt
Franklin Delano Roosevelt (; ; January 30, 1882April 12, 1945), often referred to by his initials FDR, was an American politician and attorney who served as the 32nd president of the United States from 1933 until his death in 1945. As the ...
, whose paralytic illness was generally believed to have been caused by polio). 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, 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.
A week before the announcement of the Francis Field Trial results in April 1955, Pierre Lépine at the Pasteur Institute
The Pasteur Institute (french: Institut Pasteur) is a French non-profit private foundation dedicated to the study of biology, micro-organisms, diseases, and vaccines. It is named after Louis Pasteur, who invented pasteurization and vaccines ...
in Paris had also announced an effective polio vaccine.
Safety incidents
In April 1955, soon after mass polio vaccination began in the US, the Surgeon General began to receive reports of patients who contracted paralytic polio about a week after being vaccinated with Salk polio vaccine from the Cutter pharmaceutical company, with the paralysis limited to the limb the vaccine was injected into. The Cutter vaccine had been used in vaccinating 200,000 children in the western and midwestern United States. Later investigations showed that the Cutter vaccine had caused 40,000 cases of polio, killing 10. In response the Surgeon General pulled all polio vaccines made by Cutter Laboratories from the market, but not before 250 cases of paralytic illness had occurred. Wyeth polio vaccine was also reported to have paralyzed and killed several children. It was soon discovered that some lots of Salk polio vaccine made by Cutter and Wyeth had not been properly inactivated, allowing live poliovirus into more than 100,000 doses of vaccine. In May 1955, the National Institutes of Health and Public Health Services established a Technical Committee on Poliomyelitis Vaccine to test and review all polio vaccine lots and advise the Public Health Service as to which lots should be released for public use. These incidents reduced public confidence in polio vaccine, leading to a drop in vaccination rates.
1961
At the same time that Salk was testing his vaccine, both Albert Sabin
Albert Bruce Sabin ( ; August 26, 1906 – March 3, 1993) was a Polish-American medical researcher, best known for developing the oral polio vaccine, which has played a key role in nearly eradicating the disease. In 1969–72, he served as th ...
and Hilary Koprowski continued working on developing a vaccine using live virus. During a meeting in Stockholm to discuss polio vaccines in November 1955, Sabin presented results obtained on a group of 80 volunteers, while Koprowski read a paper detailing the findings of a trial enrolling 150 people.[ Sabin and Koprowski both eventually succeeded in developing vaccines. Because of the commitment to the Salk vaccine in America, Sabin and Koprowski both did their testing outside the United States, Sabin in Mexico] and the Soviet Union, Koprowski in the Congo and Poland.[ In 1957, Sabin developed a trivalent vaccine containing attenuated strains of all three types of poliovirus.] In 1959, ten million children in the Soviet Union
The Soviet Union,. officially the Union of Soviet Socialist Republics. (USSR),. was a List of former transcontinental countries#Since 1700, transcontinental country that spanned much of Eurasia from 1922 to 1991. A flagship communist state, ...
received the Sabin oral vaccine. For this work, Sabin was given the medal of the Order of Friendship of Peoples
The Order of Friendship of Peoples (russian: oрден Дружбы народов, translit=orden Druzhby narodov) was an order of the Soviet Union, and was awarded to persons (including non-citizens), organizations, enterprises, military unit ...
, described as the Soviet Union's highest civilian honor. Sabin's oral vaccine using live virus came into commercial use in 1961.[
Once Sabin's oral vaccine became widely available, it supplanted Salk's injected vaccine, which had been tarnished in the public's opinion by the ]Cutter incident
Cutter Laboratories was a family-owned pharmaceutical company located in Berkeley, California, founded by Edward Ahern Cutter in 1897. Cutter's early products included anthrax vaccine, hog cholera (swine fever) virus, and anti-hog cholera serum— ...
of 1955, in which Salk vaccines improperly prepared by one company resulted in several children dying or becoming paralyzed.
1987
An enhanced-potency
Potency may refer to:
* Potency (pharmacology), a measure of the activity of a drug in a biological system
* Virility
* Cell potency, a measure of the differentiation potential of stem cells
* In homeopathic dilutions, potency is a measure of how ...
IPV was licensed in the United States in November 1987, and is currently the vaccine of choice there.[ The first dose of polio vaccine is given shortly after birth, usually between 1 and 2 months of age, and 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 and 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.[ 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 (five-component) combination vaccine (called Pediarix)] containing IPV was approved for use in the United States.[
]
1988
A global effort to eradicate polio, led by the World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of ...
(WHO), UNICEF
UNICEF (), originally called the United Nations International Children's Emergency Fund in full, now officially United Nations Children's Fund, is an agency of the United Nations responsible for providing humanitarian and developmental aid to ...
, and the Rotary Foundation, began in 1988, and has relied largely on the oral polio vaccine developed by Albert Sabin
Albert Bruce Sabin ( ; August 26, 1906 – March 3, 1993) was a Polish-American medical researcher, best known for developing the oral polio vaccine, which has played a key role in nearly eradicating the disease. In 1969–72, he served as th ...
and Mikhail Chumakov
Mikhail Petrovich Chumakov (russian: Михаи́л Петро́вич Чумако́в) (November 14, 1909 – June 11, 1993) was a Soviet microbiologist and virologist most famous for conducting pivotal large-scale clinical trials that led to l ...
(Sabin-Chumakov vaccine).
After 1990
Polio was eliminated in the Americas by 1994. The disease was officially eliminated in 36 Western Pacific countries, including China and Australia, in 2000. Europe was declared polio-free in 2002. Since January 2011, no cases of the disease have been reported in India, hence in February 2012, the country was taken off the WHO list of polio-endemic countries. In March 2014, India was declared a polio-free country.
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 occur, 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.[ In November 2013, the WHO announced a polio outbreak in Syria. In response, the Armenian government put out a notice asking Syrian Armenians under age 15 to get the polio vaccine. As of 2014, polio virus had spread to 10 countries, mainly in Africa, Asia, and the ]Middle East
The Middle East ( ar, الشرق الأوسط, ISO 233: ) is a geopolitical region commonly encompassing Arabia (including the Arabian Peninsula and Bahrain), Asia Minor (Asian part of Turkey except Hatay Province), East Thrace (Europ ...
, with Pakistan, Syria, and Cameroon
Cameroon (; french: Cameroun, ff, Kamerun), officially the Republic of Cameroon (french: République du Cameroun, links=no), is a country in west-central Africa. It is bordered by Nigeria to the west and north; Chad to the northeast; the C ...
advising vaccinations to outbound travellers.
Polio vaccination programs have been resisted by some people in Pakistan, Afghanistan, and Nigeria - the three countries as of 2017 with remaining polio cases. Almost all Muslim religious and political leaders have endorsed the vaccine, but a fringe minority believes that the vaccines are secretly being used for sterilization of Muslims. The fact that the CIA organized a fake vaccination program in 2011 to help find Osama Bin Laden is an additional cause of distrust. In 2015, the WHO announced a deal with the Taliban
The Taliban (; ps, طالبان, ṭālibān, lit=students or 'seekers'), which also refers to itself by its state name, the Islamic Emirate of Afghanistan, is a Deobandi Islamic fundamentalist, militant Islamist, jihadist, and Pasht ...
to encourage them to distribute the vaccine in areas they control. However, the Pakistani Taliban was not supportive. On 11 September 2016, two unidentified gunmen associated with the Pakistani Taliban, Jamaat-ul-Ahrar, shot Zakaullah Khan, a doctor who was administering polio vaccines in Pakistan. The leader of the Jamaat-ul-Ahrar claimed responsibility for the shooting and stated that the group would continue this type of attack. Such resistance to and skepticism of vaccinations has consequently slowed down the polio eradication process within the two remaining endemic countries.
Travel requirements
Travellers who wish to enter or leave certain countries must be vaccinated against polio, usually at most 12 months and at least 4 weeks before crossing the border, and be able to present a vaccination record/certificate at the border checks. Most requirements apply only to travel to or from so-called 'polio-endemic', 'polio-affected', 'polio-exporting', 'polio-transmission', or 'high-risk' countries. As of August 2020, Afghanistan and Pakistan are the only polio-endemic countries in the world (where wild polio has not yet been eradicated). Several countries have additional precautionary polio vaccination travel requirements, for example to and from 'key at-risk countries', which as of December 2020 include China, Indonesia, Mozambique, Myanmar, and Papua New Guinea.
Society and culture
Cost
, the Global Alliance for Vaccines and Immunization
GAVI, officially Gavi, the Vaccine Alliance (previously the GAVI Alliance, and before that the Global Alliance for Vaccines and Immunization) is a public–private global health partnership with the goal of increasing access to immunization ...
supplies the inactivated vaccine to developing countries for as little as (about ) per dose in 10-dose vials.
Misconceptions
A misconception has been present in Pakistan that polio vaccine contained ''haram
''Haram'' (; ar, حَرَام, , ) is an Arabic term meaning 'Forbidden'. This may refer to either something sacred to which access is not allowed to the people who are not in a state of purity or who are not initiated into the sacred knowle ...
'' ingredients and could cause impotence and infertility in male children, leading some parents not to have their children vaccinated. This belief is most common in the Khyber Pakhtunkhwa
Khyber Pakhtunkhwa (; ps, خېبر پښتونخوا; Urdu, Hindko: خیبر پختونخوا) commonly abbreviated as KP or KPK, is one of the Administrative units of Pakistan, four provinces of Pakistan. Located in the Geography of Pakistan, ...
province and the FATA
, conventional_long_name = Federally Administered Tribal Areas
, nation = Pakistan
, subdivision = Autonomous territory
, image_flag = Flag of FATA.svg
, image_coat = File:Coat of arms ...
region. Attacks on polio vaccination teams have also occurred, thereby hampering international efforts to eradicate polio in Pakistan and globally.
References
Further reading
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External links
*
History of Vaccines Website – History of Polio
History of Vaccines, a project of the College of Physicians of Philadelphia
The College of Physicians of Philadelphia is the oldest private medical society in the United States. Founded in 1787 by 24 Philadelphia physicians "to advance the Science of Medicine, and thereby lessen human misery, by investigating the disease ...
PBS.org
– 'People and Discoveries: Salk Produces Polio Vaccine 1952', Public Broadcasting Service (PBS)
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{{DEFAULTSORT:Polio Vaccine
Polio
1952 in biology
1955 introductions
American inventions
Inactivated vaccines
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World Health Organization essential medicines (vaccines)
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