In 1953 at the height of polio epidemics in the United States, Salk and colleagues described preliminary findings that led to an inactivated poliovirus vaccine. After review of the scientific evidence favoring artificial immunization against polio, the systematic experimental approach to vaccine development was outlined in detail including the criteria for selection of the vaccine strains, the choice of monkey kidney cells for vaccine virus production in tissue culture, and the inactivation of infectivity by incubation of clarified virus preparations in a 1:250 formalin at 1°C for 7 to 10 days.
Preliminary results were reported on the levels of neutralizing serum antibodies induced in 161 human participants who had been injected with the experimental vaccine just a few months earlier. Antibody levels, measured in both tissue culture and in mice, were higher when the vaccine was emulsified in a mineral oil adjuvant and delivered intramuscularly than when the vaccine was prepared in an aqueous suspension and delivered intradermally. Antibody levels to each of the 3 poliovirus serotypes induced by the inactivated vaccines compared favorably with levels induced by natural infection. Formalin inactivation of infectivity, measured by intracerebral inoculation of cynomulgus monkeys, appeared to be irreversible and the induction of neutralizing serum antibodies in human participants appeared to be entirely attributable to the noninfectious experimental vaccines.
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