A heat shock protein based polyvalent vaccine targeting HSV-2: CD4+ and CD8+ 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, Srivastava, Pramod K
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 03-11-2011; Elsevier; Elsevier Limited
• Subjects: Adjuvants, Immunologic - administration & dosage; Allergy and Immunology; Animals; Applied microbiology; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CD8-positive T-lymphocytes; CD8-Positive T-Lymphocytes - immunology; cell-mediated immunity; Cellular immunity; disease control; Disease Models, Animal; Fundamental and applied biological sciences. Psychology; Genital herpes; Guinea Pigs; Heat shock protein; Heat shock proteins; Herpes Genitalis - immunology; Herpes Genitalis - prevention & control; Herpes Genitalis - therapy; Herpes Simplex Virus Vaccines - administration & dosage; Herpes Simplex Virus Vaccines - adverse effects; Herpes Simplex Virus Vaccines - genetics; Herpes Simplex Virus Vaccines - immunology; Herpes viruses; Herpesvirus 2, Human - genetics; Herpesvirus 2, Human - immunology; HLA-A2 Antigen - genetics; HLA-A2 Antigen - immunology; HSC70 Heat-Shock Proteins - genetics; HSC70 Heat-Shock Proteins - immunology; Humans; Immunotherapy; Kinases; Leukocytes, Mononuclear - immunology; Lymphocytes; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Microbiology; Miscellaneous; Packaging; Peptides; Prophylaxis; Saponins - administration & dosage; Therapeutic vaccine; transgenic animals; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Subunit - administration & dosage; Vaccines, Subunit - genetics; Vaccines, Subunit - immunology; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - adverse effects; Vaccines, Synthetic - genetics; Vaccines, Synthetic - immunology; viral antigens; Viral Proteins - genetics; Viral Proteins - immunology; Virology; viruses; Cellular immunity; Genital herpes; Therapeutic vaccine; Heat shock protein; Immunoprotection; Targeting; Herpesviridae; Alphaherpesvirinae; Vaccine; Genital diseases; Infection; Virus; Sexually transmitted disease; Efficiency; Viral disease; Immunotherapy; Human herpesvirus 2
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2011.07.011

Abstract 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+ and CD8+ 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+ 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+ T cells from HSV-2+ 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+ subjects with the intent of eliciting CD4+ and CD8+ T cell responses to a broad array of viral antigens.