title: Safety and immunogenicity of long HSV-2 peptides complexed with rhHsc70 in HSV-2 seropositive persons.
abstract: HSV-2, the primary causative agent of genital herpes, establishes latency in sensory ganglia and reactivates causing recurrent lesions and viral shedding. Induction or expansion of CD4(+) and CD8(+) T cell responses are expected to be important for a successful therapeutic vaccine against HSV-2. A candidate vaccine consisting of 32 synthetic 35mer HSV-2 peptides non-covalently complexed with recombinant human Hsc70 protein (named HerpV, formerly AG-707) was tested for safety and immunogenicity in a Phase I study. These peptides are derived from 22 HSV-2 proteins representative of all phases of viral replication. Thirty-five HSV-2 infected participants were randomized and treated in one of four groups: HerpV+QS-21 (saponin adjuvant), HerpV, QS-21, or vehicle. The vaccine was well tolerated and safe. All seven participants with evaluable samples who were administered HerpV with QS-21 demonstrated a statistically significant CD4(+) T cell response to HSV-2 antigens, and the majority of such participants demonstrated a statistically significant CD8(+) T cell response as well. To our knowledge, this is the first candidate vaccine against HSV-2 to demonstrate a broad CD4(+) and CD8(+) T cell response in HSV-2(+) participants, and the first HSP-based vaccine to show immune responses against viral antigens in humans.
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA. annawald@u.washington.edu
authors.forename: Anna
authors.initials: A
authors.lastname: Wald
authors.forename: David M
authors.initials: DM
authors.lastname: Koelle
authors.forename: Kenneth
authors.initials: K
authors.lastname: Fife
authors.forename: Terri
authors.initials: T
authors.lastname: Warren
authors.forename: Kenneth
authors.initials: K
authors.lastname: Leclair
authors.forename: Roman M
authors.initials: RM
authors.lastname: Chicz
authors.forename: Stephen
authors.initials: S
authors.lastname: Monks
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Levey
authors.forename: Cristina
authors.initials: C
authors.lastname: Musselli
authors.forename: Pramod K
authors.initials: PK
authors.lastname: Srivastava
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D050883:HSC70 Heat-Shock Proteins / Q000235:genetics / Q000276:immunology*; D006558:Herpes Genitalis / Q000276:immunology / Q000517:prevention & control; D022301:Herpes Simplex Virus Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D050883:HSC70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D022301:Herpes Simplex Virus Vaccines; D014614:Vaccines, Synthetic; D014764:Viral Proteins