A Mouse Model for the Pathogenesis and Postexposure Prophylaxis of Rabies

Abstract

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:

Essential Role of T Cells in the Postexposure Prophylaxis of Rabies in Mice

“…The CVS strain of rabies virus passaged in suckling mouse brain was used for the production of antirabies neutralizing antibody in mice. Plaque-purified CVS strain (15) passaged in CER cells (23) was also used for the rapid fluorescent focus-inhibition test (RFFIT). The Indiana strain of vesicular stomatitis virus (VSV) was used for IF assay.…”

“…The role of cell-mediated immunity in the postexposure prophylaxis of rabies has not yet been evaluated, although recent studies demonstrated the development of a cell-mediated immune response in animals immunized either with live or with {1-propiolactone-inactivated rabies virus (13,26,27,30,31), Our previous study in mice showed that, although IF induced early after vaccination is important, postexposure prophylaxis of rabies in mice cannot be achieved only by the IF and neutralizing antibody produced by the vaccine, and suggested the requirement of some additional mechanisms (15).…”

Suppression of Cell‐Mediated Immunity by Street Rabies Virus Infection

“…immune response (20). Although high levels of virus neutralizing antibodies induced by pre-exposure vaccination play a significant role in protecting against subsequent lethal virus infection, protection by post-exposure vaccination is only achieved by vaccine and not by antibody alone (1,8,14), indicating the involvement of some other protective mechanisms. It has been suggested that the induction K. HIRAI ET AL of specific cell-mediated immunity (CMI) is a crucial factor in the protection of the host from rabies (5,9,10,15,22).…”

Murine T Cell Clones Directed to Rabies Virus: Isolation and Some of Their Properties

“…Although rabies vaccine induces the production of high levels of antibodies, prophylaxis does not always depend on the amount of antibody produced and passive administration of antibody alone is not effective in reducing the mortality of infected animals (Sikes et al, 1971 ;Baer & Yager, 1977;Mifune et al, 1980).…”