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

Vaccine. 2011 Nov 3;29(47):8530-41. doi: 10.1016/j.vaccine.2011.07.011. Epub 2011 Jul 19.


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.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Disease Models, Animal
  • Guinea Pigs
  • HLA-A2 Antigen / genetics
  • HLA-A2 Antigen / immunology
  • HSC70 Heat-Shock Proteins / genetics
  • HSC70 Heat-Shock Proteins / immunology*
  • 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*
  • Herpesvirus 2, Human / genetics
  • Herpesvirus 2, Human / immunology*
  • Humans
  • Leukocytes, Mononuclear / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Saponins / administration & dosage
  • 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 Proteins / genetics
  • Viral Proteins / immunology*


  • Adjuvants, Immunologic
  • HLA-A2 Antigen
  • HSC70 Heat-Shock Proteins
  • HSPA8 protein, human
  • Herpes Simplex Virus Vaccines
  • Saponins
  • Vaccines, Subunit
  • Vaccines, Synthetic
  • Viral Proteins