A heat shock protein based polyvalent vaccine targeting HSV-2: CD4 super(+ and CD8) super(+) cellular immunity and protective efficacy

• Published in: Vaccine Vol. 29; no. 47; pp. 8530 - 8541
• Main Authors: Mo, Annie, Musselli, Cristina, Chen, Hong, Pappas, John, LeClair, Kenneth, Liu, Aston, Chicz, Roman M, Truneh, Alemseged, Monks, Stephen, Levey, Daniel L, ivastava, Pramod K
• Format: Journal Article
• Language: English
• Published: 03.11.2011
• Subjects: Herpes simplex virus 2
• ISSN: 0264-410X
• DOI: 10.1016/j.vaccine.2011.07.011

Efforts to develop a subunit vaccine against genital herpes have been hampered by lack of knowledge of the protective antigens of HSV-2, the causative agent of the disease. Vaccines based either on selected antigens or attenuated live virus approaches have not demonstrated meaningful clinical activity. We present here results of a therapeutic vaccine candidate, HerpV (formerly called AG-707), consisting of 32 HSV-2 peptides derived from 22 HSV-2 proteins, complexed non-covalently to the HSP70 chaperone and formulated with QS-21 saponin adjuvant. HerpV is observed to be immunogenic, generating CD4 super(+ and CD8) super(+) T cell responses in three mouse strains including HLA-A2 transgenic mice. Optimal T cell stimulation was dependent on the synergistic adjuvant properties of QS-21 with hsp70. The vaccine provided significant protection from viral challenge in a mouse prophylaxis model and showed signals of activity in a guinea pig therapeutic model of existing infection. Peripheral blood mononuclear cells from human HSV-2 super(+ subjects also showed reactivity in vitro to a subset of individual peptides and to the pool of all 32 peptides. Recombinant human Hsc70 complexed with the 32 peptides also stimulated the expansion of CD8) super(+) T cells from HSV-2 super(+ subjects in vitro. These studies demonstrate that HerpV is a promising immunotherapy candidate for genital herpes, and provide a foundation for evaluating HerpV in human HSV-2) super(+) subjects with the intent of eliciting CD4 super(+ and CD8) super(+) T cell responses to a broad array of viral antigens.