Safety and immunogenicity of long HSV-2 peptides complexed with rhHsc70 in HSV-2 seropositive persons

Anna Wald, David M. Koelle, Kenneth Fife, Terri Warren, Kenneth LeClair, Roman M. Chicz, Stephen Monks, Daniel L. Levey, Cristina Musselli, Pramod K. Srivastava

Research output: Contribution to journalArticle

45 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)8520-8529
Number of pages10
JournalVaccine
Volume29
Issue number47
DOIs
StatePublished - Nov 3 2011

Fingerprint

Human Herpesvirus 2
immune response
peptides
vaccines
Safety
T-lymphocytes
Peptides
Vaccines
T-Lymphocytes
viral shedding
viral antigens
virus replication
saponins
HSC70 Heat-Shock Proteins
lesions (animal)
genitalia
adjuvants
Sensory Ganglia
Virus Shedding
Herpes Genitalis

Keywords

  • CD8 T cell
  • Genital herpes
  • Heat shock protein
  • Therapeutic vaccine

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

Cite this

Wald, A., Koelle, D. M., Fife, K., Warren, T., LeClair, K., Chicz, R. M., ... Srivastava, P. K. (2011). Safety and immunogenicity of long HSV-2 peptides complexed with rhHsc70 in HSV-2 seropositive persons. Vaccine, 29(47), 8520-8529. https://doi.org/10.1016/j.vaccine.2011.09.046

Safety and immunogenicity of long HSV-2 peptides complexed with rhHsc70 in HSV-2 seropositive persons. / Wald, Anna; Koelle, David M.; Fife, Kenneth; Warren, Terri; LeClair, Kenneth; Chicz, Roman M.; Monks, Stephen; Levey, Daniel L.; Musselli, Cristina; Srivastava, Pramod K.

In: Vaccine, Vol. 29, No. 47, 03.11.2011, p. 8520-8529.

Research output: Contribution to journalArticle

Wald, A, Koelle, DM, Fife, K, Warren, T, LeClair, K, Chicz, RM, Monks, S, Levey, DL, Musselli, C & Srivastava, PK 2011, 'Safety and immunogenicity of long HSV-2 peptides complexed with rhHsc70 in HSV-2 seropositive persons', Vaccine, vol. 29, no. 47, pp. 8520-8529. https://doi.org/10.1016/j.vaccine.2011.09.046
Wald, Anna ; Koelle, David M. ; Fife, Kenneth ; Warren, Terri ; LeClair, Kenneth ; Chicz, Roman M. ; Monks, Stephen ; Levey, Daniel L. ; Musselli, Cristina ; Srivastava, Pramod K. / Safety and immunogenicity of long HSV-2 peptides complexed with rhHsc70 in HSV-2 seropositive persons. In: Vaccine. 2011 ; Vol. 29, No. 47. pp. 8520-8529.
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