Experimental study of the role of inactivated vaccine in two-step vaccination against smallpox

In experiments on rabbits it was found that although administration of inactivated smallpox vaccine did not induce a demonstrable antibody response in the serum it enhanced the immune response to subsequent inoculation with live vaccine. The dose of inactivated vaccine corresponded to 8 x 10(7) PFU before inactivation (by (60)Co gamma-radiation); the dose of live vaccine was 1.2 x 10(5) PFU. When the interval between the two inoculations was 7-days, virus-neutralizing antibody appeared after 5 days and reached levels 2-4 times those obtained with live vaccine alone. With longer intervals (up to 60 days) the enhancement of the immune response was even greater. It seems likely that use of the two-step method may reduce the incidence of post-vaccination encephalitis and clinical studies to determine the optimum conditions for safety and efficacy are at present being undertaken.