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Portions of the work reported here were performed under Project 4Bl1-05-015, "Protective Measures for Personnel in the BW Program,"Task -02," Clinical Investigations Related to R&D Hazards." The expenditure order was 2022. This information was originally submitted as manuscript 5294.The information in this document has not been cleared for release to the public. DDC AVAILABILITY NOTICEQualified requestors may obtain copies of this document from DDC.Foreign announcement and dissemination of this document by DDC is limited. 3ABSTRACT A streptomycin-dependent mutant of Salmonella typhosa injected live in rabbits stimulated the production of 0 antibodies.Sera from these rabbits protected mice against challenge with virulent S. typhosa. Mutation to the dependent state did not result in loss of antigenicity. Streptomycin dependency of the mutant was demonstrated in vivo in the mouse.Antibiotic-treated mice succumbed to challenge with dependent bacilli, apparently because of presence of lethal quantities of endotoxin produced by multiplication of the mutant in the presence of streptomycin.

The efficacy of Formalin-inactivated Venezuelan equine encephalitis (VEE) vaccine has been reported to be low for man. Although a live VEE vaccine has been shown to be highly effective for the protection of laboratory workers, local and systemic reactions have occurred in approximately 20% of inoculated individuals. Therefore, studies were initiated in an attempt to produce an inactivated vaccine of high potency with low toxicity. Inactivated VEE vaccines were prepared by exposing virus suspensions to 8 x 106 or 10 X 106 r of gamma radiation. Irradiated VEE vaccines prepared from virus suspensions produced in Maitland-type chick embryo (MTCE) cell cultures and in monolayer cultures of human diploid strain WI-38 cells were highly immunogenic for mice and guinea pigs. Guinea pigs vaccinated with a series of three inoculations of vaccine (MTCE) survived challenge with at least 108.4 mouse intracerebral 50% lethal doses of VEE virus. Irradiated vaccines induced high levels of serum-neutralizing and hemagglutinin-inhibiting antibodies in guinea pigs and rabbits. These findings suggest that ionizing radiation may be effective in the preparation of an inactivated VEE vaccine.

Exposure of Venezuelan equine encephalomyelitis (VEE) virus (at-70 C) to 6 x 106 r y-radiation (6WCo) resulted in loss of lethality for young adult mice and guinea pigs, and loss of capacity to produce plaques or cyLopathic effects in tissue culture. The suckling mouse was more sensitive for detecting live virus in radiated suspensions than was the adult mouse or guinea pig. Live virus was demonstrable in preparations exposed to 6 X 106 r but not in suspensions exposed to 8 X 106 r and more. The rate of inactivation of VEE virus by 7-radiation was an exponential function of the dosage.

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