Highly Attenuated Rabies Virus Based Vaccine Vectors Expressing Simian-Human Immunodeficiency$Virus_{89.6P}$, Env and Simian Immunodeficiency$Virus_{mac239}$Gag Are Safe in Rhesus Macaques and Protect from an AIDS-like Disease

We analyzed the safety and immunogenicity of attenuated rabies virus vectors expressing simian-human immunodeficiency virus$(SHIV)-1_{89.6P}$, Env or simian immunodeficiency virus$(SIV)_{mac239}$Gag in rhesus macaques. Four test macaques were immunized with both vaccine constructs, and 2 control mac...

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Bibliographic Details
Published in:The Journal of infectious diseases 2007-04, Vol.195 (7), p.980-988
Main Authors: McKenna, Philip M., Koser, Martin L., Carlson, Kevin R., Montefiori, David C., Letvin, Norman L., Papaneri, Amy B., Pomerantz, Roger J., Dietzschold, Bernhard, Silvera, Peter, McGettigan, James P., Schnell, Matthias J.
Format: Article
Language:English
Subjects:
AIDS
Antibodies
HIV 1
HIV/AIDS
Infections
Neutralizing antibodies
Rabies
Rabies virus
T lymphocytes
Vaccination
Viruses
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Summary:We analyzed the safety and immunogenicity of attenuated rabies virus vectors expressing simian-human immunodeficiency virus$(SHIV)-1_{89.6P}$, Env or simian immunodeficiency virus$(SIV)_{mac239}$Gag in rhesus macaques. Four test macaques were immunized with both vaccine constructs, and 2 control macaques received an empty rabies vector. Seroconversion against rabies virus glycoprotein (G) and$SHIV_{89.6P}$, Env was detected after the initial immunization, but no cellular responses against SHIV antigens were observed. HIV/SIV-specific immune responses were not enhanced by boosts with the same vectors. Therefore, we constructed vectors expressing$SHIV_{89.6P}$Env and$SIV_{mac239}$Gag in which the rabies G was replaced with the G protein of vesicular stomatitis virus (VSV). Two years after initial immunization, a boost with the rabies-VSV G vectors resulted in SIV/HIV-specific immune responses. Upon challenge with$SHIV_{89.6P}$test macaques controlled the infection, whereas control macaques had high levels of viremia and a profound loss of CD4⁺ T cells, with 1 control macaque dying of an AIDS-like disease.
ISSN:0022-1899
1537-6613
DOI:10.1086/512243