Vaccination of rhesus macaques with a vif-deleted simian immunodeficiency virus proviral DNA vaccine
- Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95616 (United States)
- Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, CA 95616 (United States)
- Center for Vaccine Research, Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 (United States)
- Center for Comparative Medicine, University of California, Davis, CA 95616 (United States)
Studies in non-human primates, with simian immunodeficiency virus (SIV) and simian/human immunodeficiency virus (SHIV) have demonstrated that live-attenuated viral vaccines are highly effective; however these vaccine viruses maintain a low level of pathogenicity. Lentivirus attenuation associated with deletion of the viral vif gene carries a significantly reduced risk for pathogenicity, while retaining the potential for virus replication of low magnitude in the host. This report describes a vif-deleted simian immunodeficiency virus (SIV)mac239 provirus that was tested as an attenuated proviral DNA vaccine by inoculation of female rhesus macaques. SIV-specific interferon-{gamma} enzyme-linked immunospot responses of low magnitude were observed after immunization with plasmid containing the vif-deleted SIV provirus. However, vaccinated animals displayed strong sustained virus-specific T cell proliferative responses and increasing antiviral antibody titers. These immune responses suggested either persistent vaccine plasmid expression or low level replication of vif-deleted SIV in the host. Immunized and unvaccinated macaques received a single high dose vaginal challenge with pathogenic SIVmac251. A transient suppression of challenge virus load and a greater median survival time was observed for vaccinated animals. However, virus loads for vaccinated and unvaccinated macaques were comparable by twenty weeks after challenge and overall survival curves for the two groups were not significantly different. Thus, a vif-deleted SIVmac239 proviral DNA vaccine is immunogenic and capable of inducing a transient suppression of pathogenic challenge virus, despite severe attenuation of the vaccine virus.
- OSTI ID:
- 21140978
- Journal Information:
- Virology, Vol. 374, Issue 2; Other Information: DOI: 10.1016/j.virol.2008.01.020; PII: S0042-6822(08)00047-0; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
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