Oral Vaccination against Tularemia in the Monkey 1

Abstract

Summary

Studies on the immunogenicity of live tularemia vaccine for animals and man vaccinated dermally or aerogenically were sufficiently encouraging to warrant an evaluation of vaccination of the monkey via the oral route. A preliminary investigation of the oral infectivity and virulence of P. tularensis SCHU S4, fatal for the monkey infected dermally or by the respiratory route with 10-25 organisms, revealed that 10⁴ viable cells swallowed with milk did not result in infection but that 10⁶ organisms infected two of eight animals, both of which died. An oral dose of 10⁸ or 10¹⁰ cells infected all monkeys tested and the majority died; severe inflammation and ulceration of the gastrointestinal tract were found at necropsy. The course and outcome of the disease were comparable when animals were compelled to swallow intact a gelatin capsule containing 10¹⁰ organisms.

In a study on the reactivity and immunogenicity of live vaccine strains LVS and of strain 425, highly infectious but seldom lethal for the monkey inoculated dermally or inhaling up to 10⁴ cells, groups of animals were force fed 10¹⁰ live organisms in milk. An additional group of monkeys was vaccinated dermally with strain LVS administered by multiple puncture. Both the oral and the dermal inocula of LVS proved innocuous but the majority of the animals given strain 425 showed a transient low grade febrile response. The sera of all vaccinees gave positive agglutinin and precipitin reactions. Ten weeks after vaccination those animals and a group of nonvaccinated controls were administered an aerogenic challenge of 10⁴ organisms of strain SCHU S4. All animals became infected but 64-71% of the vaccinees survived in contrast to 14% of the nonvaccinated controls. A potential for oral vaccination with live tularemia vaccine prepared from strain LVS was demonstrated by these studies and led to tests in volunteers which showed that vaccination with strain LVS by the oral route is useful and practical for the immunization of man against tularemia (7).