Virology

Biography

Biography: Sita Awasthi

Abstract

About 500 million people are infected with Herpes Simplex Virus type 2 (HSV-2) worldwide. Genital HSV-2 infection is one of the major causes of genital ulcer disease and the risk of HIV-1 acquisition and transmission by 3-4 fold in humans. Efforts to prevent genital ulcer disease with acyclovir failed to reduce HIV-1 acquisition or transmission, supporting the need for an effective vaccine. We developed a trivalent gC2/gD2/gE2 (HSV-2 glycoprotein C, D and E) subunit vaccine that generates high levels of neutralizing antibodies, blocks HSV-2 immune evasion from complement, blocks IgG-Fc binding to the HSV-2 IgG Fc receptor, and is highly efficacious in preventing genital disease and viral shedding in guinea pigs. Here we present an immunogenicity evaluation of gC2/gD2/gE2 vaccine in macaques. Female macaques were immunized three times four weeks apart with 20g of each gC2, gD2, and gE2 glycoprotein or 20g gC2 alone with CpG and alum as adjuvants. After the third immunization, plasma analysis showed high titer antibody responses to each antigen, high titer neutralizing antibodies, and antibodies that blocked complement C3b binding to gC2 and IgG Fc binding to gE2. Six months after the third vaccination, the immune responses to each glycoprotein had declined 2-3 fold, but boosted within 2-weeks after a booster immunization administered at 9 months. Additionally we detected antigen specific antibody response in vaginal fluid. Importantly, analysis of PBMCs from macaques that were immunized with gC2 alone, showed a gC2 specific CD8 T cell response after 3 immunizations. In addition, antigen specific poly-functional CD4 T cell responses are induced in the trivalent vaccine group. Our results show that the trivalent gC2/gD2/gE2 subunit antigen vaccine generates highly potent immune responses in Rhesus macaques and may prove to be a promising genital herpes vaccine candidate for future trials in human.