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

Abstract

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. In the present study, a new strategy to improve live-attenuated SHIV was examined by genetically engineered virus that co-expresses an immunostimulatory molecule Ag85B such as an adjuvant. We genetically constructed a live nef-deleted simian-human immunodeficiency virus to express the adjuvant molecule Ag85B (SHIV-Ag85B) and assessed vaccine effects in cynomolgus macaques. The 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. Moreover, most of macaques inoculated with SHIV-Ag85B showed protective effects against the intravenous challenge of pathogenic SHIV89.6P, and viral RNAs remained undetectable for more than 200 weeks. Remarkably, eradication of SHIV89.6P was confirmed by an adoptive transfer experiment and CD8+ cell depletion study. In these macaques, SHIV antigen-specific CD8+ T cell responses with polyfunctionality were rapidly induced in the acute phase of SHIV89.6P 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 live vaccine and cure for AIDS virus infection. Supported by Health Science Research Grants from the Ministry of Health, Labor and Welfare of Japan, Ministry of Education, Culture, Sports, Science and Technology, Japan, Japan Agency for Medical Research and Development, AMED (19ak0101047h0004, 19fk0410025h0001, 19ak0101068h0003 and 19fk0410011h0702).