Long term sterile immunity induced by an adjuvant-containing live-attenuated AIDS virus

Abstract

Antigen 85B (Ag85B) is one of the most dominant proteins secreted from most mycobacterial species, and it induces Th1-type immune responses as an adjuvant. We genetically constructed a live attenuated simian human immunodeficiency virus to express the adjuvant molecule Ag85B (SHIV-Ag85B). SHIV-Ag85B could not be detected 4 weeks after injection in cynomolgus macaques, and strong SHIV-specific T cell responses were induced in these macaques. When these macaques in which SHIV-Ag85B had become undetectable were challenged with pathogenic SHIV89.6P at 37 weeks after SHIV-Ag85B became undetectable, SHIV89.6P could not be detected after the challenge. Eradication of SHIV89.6P was confirmed by adoptive transfer experiments and CD8-depletion studies. The SHIV-Ag85B-inoculated macaques showed enhancement of Gag-specific monofunctional and polyfunctional CD8+ T cells in the acute phase of pathogenic SHIV challenge. The results suggest that SHIV-Ag85B elicited strong sterile immune responses against pathogenic SHIV and that it may lead to the development of a vaccine for AIDS virus infection. ImportanceDevelopment of an effective HIV vaccine has been a major priority to control the worldwide AIDS epidemic. The moderately attenuated prototypic vaccine strain SIVmac239{Delta}nef has been used in various studies; however, it does not provide sufficient effects to prevent infection. The use of adjuvant in vaccination is thought to be useful for enhancing the immune responses to various pathogens. In the present study, we constructed a live attenuated SHIV virus expressing adjuvant molecule Ag85B and assessed vaccine effects in cynomolgus macaques. The present study shows that live-attenuated SHIV expressing Ag85B elicits viral antigen-specific polyfunctional CD8+ T cell responses against pathogenic SHIV and provide the possibility of eradicating a pathogenic lentivirus from infected animals.