Ethan Poteet, Phoebe Lewis, Zhiyin Yu,Changyi Chen, Guojun Yang, Pramod N Nehete, K Jagannadha Sastry, Gary Fujii, Qizhi Yao
Simian/Human immunodeficiency virus (SHIV) virus-like particles (VLPs) composed of SIV Gag, HIVsf162 gp120/ gp41 envelope, and human CD40L are whole pseudovirion vaccines capable of eliciting both humoral and cellular immunity. We immunized four rhesus macaques by intranasal prime and four sub-cheek boosts with VLPs adjuvanted with conjugatable adjuvant lipid vesicles containing monophosphoryl lipid A (MPLA), and compared their immune parameters to those in five unimmunized control macaques. Increased plasma antibody titers to SIV Gag were observed in all four immunized macaques and increased sf162 gp140 titers were observed in three of the four with one macaque (10-195) maintaining sustained anti-Env antibody levels. Compared to controls, a significant increase in memory B cells and CD4+ central memory T cells was detected in the immunized group. Among these, elevated Gagspecific CD107a membrane localization in the CD8+ central memory T cells was detected in one macaque (10-195). All nine macaques were subsequently challenged intrarectally with SHIVsf162.P3. After challenge, eight of the nine macaques became infected with SHIV, while the macaque 10-195 was protected. Another immunized macaque (10-189) that got infected but consequently generated high Gag-specific IFN-γ and CD107a CD8+ T cells; and Envspecific IL-2 and CD107a CD8+ T cells controlled virus and had undetectable levels of plasma SIV copy number by the termination of the study. Our VLPs vaccine strategy represents a promising immunogenic conformationally intact HIV vaccine that may lead to possible prevention and control of HIV infection.