RECOMBINANT VACCINE-INDUCED PROTECTION AGAINST THE HIGHLY PATHOGENIC SIMIAN IMMUNODEFICIENCY VIRUS SIVMAC251 - DEPENDENCE ON ROUTE OF CHALLENGE EXPOSURE

Vaccine protection from infection and/or disease induced by highly pat hogenic simian immunodeficiency virus (SIV) strain SIVmac251 in the rh esus macaque model is a challenging task Thus far, the only approach t hat has been reported to protect a fraction of macaques from infection following intravenous challenge with SIVmac251 was the use of a live attenuated SIV vaccine. In the present study, the gag, pol, and env ge nes of SIVK6W were expressed in the NYVAC vector, a genetically engine ered derivative of the vaccinia virus Copenhagen strain that displays a highly attenuated phenotype in humans. In addition, the genes for th e alpha and beta chains of interleukin-12 (IL-12), as well as the IL-2 gene, were expressed in separate NYVAC vectors and inoculated intramu scularly, in conjunction with or separate from the NYVAC-SIV vaccine, in 40 macaques. The overall cytotoxic T-lymphocyte (CTL) response was greater, at the expense of proliferative and humoral responses, in ani mals immunized with NYVAC-SIV and NYVAC-IL-12 than in animals immunize d with the NYVAC-SIV vaccine alone. At the end of the immunization reg imen, half of the animals were challenged with SIVmac251 by the intrav enous route and the other half were exposed to SIVmac251 intrarectally . Significantly, five of the eleven vaccinees exposed mucosally to SIV mac251 showed a transient peak of viremia 1 week after viral challenge and subsequently appeared to clear viral infection. In contrast, all 12 animals inoculated intravenously became infected, but 5 to 6 months after viral challenge, 4 animals were able to control viral expressio n and appeared to progress to disease more slowly than control animals . Protection did not appear to be associated with any of the measured immunological parameters, Further modulation of immune responses by co administration of NYVAC-cytokine recombinants did not appear to influe nce the outcome of viral challenge. The fact that the NYVAC-SIV recomb inant vaccine appears to be effective per se in the animal model that best mirrors human AIDS supports the idea that the development of a hi ghly attenuated poxvirus-based vaccine candidate can be a valuable app roach to significantly decrease the spread of human immunodeficiency v irus (HIV) infection by the mucosal route.