A mouse model for the study of postexposure prophylaxis of rabies was established. Mice injected intramuscularly with a street strain of rabies virus were significantly protected from death by five daily 0.2-ml doses of inactivated rabies vaccine of chick embryo cell culture origin initiated immediately or 3 hr after infection. In these mice, a large amount of circulating interferon was induced as early as 1 hr after the first dose of vaccine and lasted until at least 12 hr but no such amount of interferon was induced by additional doses of vaccine.Serum antibody was first detected in the mice on day 6. It was noted that some of the surviving mice manifested an ataxia or paralysis of the legs. Increasing mortality rates were shown in mice treated with decreasing doses of the vaccine.Passive protection tests using concentrated IgG and IgM antibodies with equivalent neutralization titers showed that IgG antibody gave total protection when given 24 hr before the infection, while it was almost totally ineffective in reducing the mortality when given 2 days or more after infection.IgM antibody did not protect the mice even when given 24 hr before infection.These results suggest that interferon production is more important than antibody production in the initial stages of protection by postexposure vaccination.However, the mechanisms of postexposure prophylaxis in this model could not be explained only by the interferon produced by the vaccine and the possible contributions of additional mechanisms were suggested.Recent studies with experimental animals have shown that postexposure administration antibody or exogenous interferon in combination with rabies vaccine (1-3) or endogenous interferon induced by rabies vaccine (1, 24) or by polyriboinosinic-polyribocytidylic acid (5, 6, 8) can be highly effective in the prophylaxis of rabies. In most of those studies, the prophylaxis did not depend on the amount of antirabies neutralizing antibody induced by the vaccine. However, the detailed role of antibody or interferon which is administered or induced by vaccine still remains unclear. A recent report states that hyperimmune antiserum passively transferred after infection with virus did not reduce the mortality but merely 1* Present address:

Athymic nude mice injected intramuscularly with a street strain of rabies virus were not protected against rabies by postexposure administration of beta-propiolactone-inactivated rabies vaccine. In contrast, their normallittermates were completely protected from death by the same vaccination regimens. Nude mice did not produce IgG antibody as a result of the vaccine during the test period of 15 days, whereas normal littermates produced IgG antibody from day 5 after vaccination. However, passive immunization with antirabies hyperimmune mouse ascites showed that antibody was completely ineffective in protecting either nude mice or their normal littermates against rabies when given later than 2 days after infection. No significant difference in the induction of circulating interferon by the vaccination was noted in these mice. Passive transfer of immune spleen 'cells to nude mice immediately after infection resulted in 30 to 37.5% protection of the mice. Passively transferred spleen cells did not produce detectable amounts of neutralizing antibody in the recipient mice except on day 2 after the transfer, when a low level of antibody was detected. These observations demonstrate the essential role of T cells in the postexposure prophylaxis of rabies in mice. The mechanisms of the failure of postexposure vaccination in nude mice are discussed.Recent studies in experimental animals have demonstrated the importance of both humoral and cell-mediated immune responses in recovery from primary rabies infection (16,24). However, the mechanisms of postexposure prophylaxis of rabies still remain unclear. Various studies have shown that interferon (IF) induced by rabies vaccine or administration of IF or IF inducers in combination with rabies vaccine can be highly effective in the prophylaxis of rabies (1-3, 17, 32), while the rabies vaccine which induces only neutralizing antibody is not effective, and the prophylaxis does not always depend on the amount of antirabies neutralizing antibody produced by the vaccine (3, 22).The role of cell-mediated immunity in the postexposure prophylaxis of rabies has not yet been evaluated, although recent studies demonstrated the development

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