This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In past studies the effectiveness of a prime-boost protocol using attenuated vesicular stomatitis virus (VSV) vectors expressing SHIV Env, Gab, and Pol proteins was compared to a VSV vector prime followed with a single boost with modified vaccinia Ankara (MVA) expressing the same SHIV proteins. This approach used an unrelated vector (MVA) to boost SHIV immunity. After challenge with SHIV89.6P, MVA-boosted animals controlled peak challenge viral loads to less than 2x106 copies/ml, significantly lower than in VSV-boosted animals, and lower than reported in other vaccine studies employing the same challenge. MVA-boosted animals have shown excellent preservation of CD4+ T cells while 2 of 4 VSV-boosted animals showed significant loss of CD4+ T cells. The improved protection in MVA-boosted animals correlates with stronger pre-challenge CD8+ T cell responses to SHIV antigens and with stronger post-challenge SHIV neutralizing antibody production. This immunization strategy of using unrelated vectors for prime and boosting was tested using SIVmac251 as the challenge virus. SIVmac251 is viewed as a more rigorous test of a vaccine than SHIV. Chinese origin and Indian origin Rhesus macaques were used for comparison in 2 separate studies. Indian rhesus were immunized with VSV vectors and boosted with MVA vectors that express multiple SIV genes. Results showed that the SIVmac251 plasma virus load was effectively controlled in the acute stage of the infection. Peak virus loads were lower in the first 30 days of the experiment in immunized monkeys compared to controls. However, the plasma viral loads were not significantly different in the groups by 90 to 180 days post-challenge. Progression to AIDS was also not slowed by the vaccination protocol. The results point to the difficulty in controlling infection against highly pathogenic SIVmac infections. Other challenge models may be more appropriate.
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