|
Page: The "great race"
Main article
| Home > Child Health > The "great race" |
In 1935 Maurice Brodie, a research assistant at New York University, had attempted to produce a polio vaccine, procured from ground up monkey spinal cords, and killed by formaldehyde. His initial attempts to develop a vaccine 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 developed allergic reactions, but none developed immunity to polio.[5] Philadelphia pathologist John Kollmer also claimed to have developed a vaccine that same year, but it too produced no immunity and was blamed for causing a number of cases, some of them fatal.
A breakthrough came in 1948 when a research group headed by John Enders at the Children's Hospital Boston successfully cultivated the poliovirus in human tissue in the laboratory. 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 for their labors with a Nobel Prize in Physiology or Medicine in 1954. Other important advancements that lead 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 preceding 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, up from a typical number of around 20,000 cases 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. Polish-born virologist and immunologist Hilary Koprowski, who also worked at Lederle, claims to have created the first successful polio vaccine (in 1950) but his vaccine, 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 inject-able vaccine) reached the market. The samples of difficult-to-manufacture attenuated virus Albert Sabin would use to develop his oral polio vaccine were given to him by Hilary Koprowski. "Koprowski would later complain that the polio vaccine he had discovered became known as the Sabin vaccine." Koprowski's own vaccine was ultimately tested, but the outcome was a failure. After the attenuated live virus entered the body, it sometimes reverted to a virulent state. Nevertheless, from 1957 to 1960, large scale tests were carried out in the Congo. The results have been controversial.
The development of two polio vaccines would lead to the first modern mass inoculations. The last cases of paralytic poliomyelitis caused by endemic transmission of wild virus in the United States were in 1979, when an outbreak occurred among the Amish in several Midwest states. The disease was entirely eradicated in the Americas by 1994.
Salk's "inactivated polio vaccine"
The first effective polio vaccine was developed in 1952 by Jonas Salk at the University of Pittsburgh. 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 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 progress to viremia and protects the motor neurons, thus eliminating the risk of bulbar polio and post-polio syndrome. However, because it offers no protection to the mucosal lining of the intestine, people vaccinated with Salk's vaccine can still carry the disease and spread it to unvaccinated individuals.
Salk's vaccine was licensed in 1955, and immediately children's vaccination campaigns were launched. In 1954, the vaccine was tested at Arsenal Elementary School and the Watson Home for Children in Pittsburgh, Pennsylvania. Salk's vaccine was then used in a test called the Francis Field Trial, led by Thomas Francis; the largest medical experiment in history. The test began with some 4,000 children at Franklin Sherman Elementary School in McLean, Virginia, and would eventually involve 1.8 million children, in 44 states from Maine to California. By the conclusion of the study, roughly 440,000 received one or more injections of the vaccine, about 210,000 children received a placebo, 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 Roosevelt). 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. In the U.S, following a mass immunization campaign promoted by the March of Dimes, the annual number of polio cases would fall to 5,600 by 1957. The IPV vaccine was used extensively in the U.S. until the early 1960s. An enhanced-potency IPV was licensed in the United States in November 1987, and is currently the vaccine of choice in the United States.
Sabin's "oral polio vaccine"
Eight years after Salk's success, Albert Sabin developed the oral polio vaccine (OPV). The 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.
There are 57 nucleotide substitutions which distinguish the attenuated Sabin 1 strain from it's virulent parent (the Mahoney serotype), two nucleotide substitutions attenuate the Sabin 2 stain, 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 (or IRES) which alters stem-loop structures, and reduces the ability of poliovirus to translate it's 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 tissue. The OPV proved to be superior in administration, and also provided longer lasting immunity than the Salk vaccine. Although Salk's vaccine had reduced the incidence of polio to a tiny fraction of what it was in the early 1950s, it would be the oral live-virus vaccine that would enable the complete elimination of the wild polio virus in the United States.
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 was licensed, and would become the vaccine of choice in the United States and most other countries of the world, largely replacing the use of the inactivated polio vaccine. A second wave of mass immunizations would lead to a dramatic decline in the number of polio cases. In 1961, only 161 cases were recorded in the United States.
|
Important notice:
The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other
qualified health provider with any questions you may have regarding a medical condition.
|