A Mouse Model for Post-Exposure Rabies Prophylaxis: The Comparative Efficacy of Two Vaccines and of Antiserum Administration

Microbiology and Immunology

Takeuchi

Napiorkowski

et al. 1981

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

Section: E;ffect If Transfer Of Immune Spleen Cells On the Outcome Ofmentioning

confidence: 99%

Section: Production Of Circulating If In Vaccinated Micementioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

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

Microbiology and Immunology

Takeuchi

Napiorkowski

et al. 1981

“…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).…”

mentioning

confidence: 99%

Suppression of Cell‐Mediated Immunity by Street Rabies Virus Infection

Hirai

Kawano

Microbiology and Immunology

et al. 1992

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Cho

Narahara

Journal of General Virology

et al. 1987

SUMMARYSeventeen Thy-14 cell clones were induced in A/J mice immunized with the HEPFlury strain of rabies virus after repeated stimulations with antigens in vitro. Ten clones with cell surface phenotypes Thy-14, Lyt-l-,2 + were cytotoxic T lymphocytes (CTL) which lysed the virus-infected target cells under H-2 restriction. Target cells expressed the G and M2 structural proteins of rabies virus on their surface; however, target lysis by CTL clones was not blocked by anti-rabies antibody or by monoclonal antibodies to these proteins. All of the CTL clones efficiently and equally lysed target cells infected with three different strains of rabies virus and were cross-reactive for target cells infected with one (Duvenhage virus) of three different rabies serogroup viruses. Another five clones having phenotype Thy-14, Lyt-14,2 -did not show any cytotoxic activity. The proliferation response of these clones to antigen stimulation was virusspecific and H-2-restricted. These clones were able to grow in culture medium without any or with the addition of low concentrations of T cell growth factor, in contrast to CTL clones, and were considered to be helper T lymphocytes (HTL). Both CTL and HTL clones produced ,/-interferon in response to antigen stimulation. The remaining two clones were Thy-1 +, Lyt-1-,2-, asialo-G M 14, and were not cytotoxic to target cells even in the presence of anti-rabies antibody but were cytotoxic to YAC-1 cells. Further studies with these clones should allow us to investigate more closely the role of T cells in the pathogenesis of rabies.