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. This Program Project seeks to develop combination immunoprophylaxis against maternal HIV clade C transmission, using a cocktail of human nmAbs and DNA prime/protein boost vaccination. These strategies are being tested in primates in Core C at Yerkes. The initial vaccinations, given to newborn monkeys, consisted of DNA encoding various genes of an HIV-like virus, called SHIVenvC, which can infect monkeys. We had constructed this virus in earlier years; it contains the envelope gene from an HIV clade C isolated from an African infant. In the second part of the vaccine studies, the vaccinated animals were inoculated with protein components of SHIVenvC. We also tested if we could generate broadly-reactive immunity against multiple AIDS viruses by inoculating one group of animals with protein components derived from a different type of SHIV. Both virus-directed antibody responses and cellular immune responses are generally regarded as important to prevent AIDS virus infection; both types of immune responses were generated in our vaccinated animals. One set of vaccinated animals was challenged with SHIVenvC; half of them strongly controlled virus infection. When these animals were later rechallenged with the more potent version of SHIVenvC, one of the vaccinated animals remained virus-free and the others had lower levels of virus than unvaccinated controls. The second set of the vaccinated animals was only challenged with the more potent version of SHIVenvC; vaccination appeared to have significantly reduced virus infection in this set of vaccine recipients. These encouraging results suggest that our vaccination approach to prevent HIV clade C infection in infants is worthwhile pursuing. Lastly, we followed the genetic changes in SHIVenvC as it became more virulent. These molecular studies will yield a better understand of viral evolution.
Showing the most recent 10 out of 912 publications
