A Randomized, Double-Blinded, Placebo-Controlled, Phase 1 Study of a Replication-Defective Herpes Simplex Virus (HSV) Type 2 Vaccine, HSV529, in Adults With or Without HSV Infection

J Infect Dis. 2019 Aug 9;220(6):990-1000. doi: 10.1093/infdis/jiz225.


Background: Herpes simplex virus 2 (HSV2) causes genital herpes in >400 million persons worldwide.

Methods: We conducted a randomized, double-blinded, placebo-controlled trial of a replication-defective HSV2 vaccine, HSV529. Twenty adults were enrolled in each of 3 serogroups of individuals: those negative for both HSV1 and HSV2 (HSV1-/HSV2-), those positive or negative for HSV1 and positive for HSV2 (HSV1±/HSV2+), and those positive for HSV1 and negative for HSV2 (HSV1+/HSV2-). Sixty participants received vaccine or placebo at 0, 1, and 6 months. The primary end point was the frequency of solicited local and systemic reactions to vaccination.

Results: Eighty-nine percent of vaccinees experienced mild-to-moderate solicited injection site reactions, compared with 47% of placebo recipients (95% confidence interval [CI], 12.9%-67.6%; P = .006). Sixty-four percent of vaccinees experienced systemic reactions, compared with 53% of placebo recipients (95% CI, -17.9% to 40.2%; P = .44). Seventy-eight percent of HSV1-/HSV2- vaccine recipients had a ≥4-fold increase in neutralizing antibody titer after 3 doses of vaccine, whereas none of the participants in the other serogroups had such responses. HSV2-specific CD4+ T-cell responses were detected in 36%, 46%, and 27% of HSV1-/HSV2-, HSV1±/HSV2+, and HSV1+/HSV2- participants, respectively, 1 month after the third dose of vaccine, and CD8+ T-cell responses were detected in 14%, 8%, and 18% of participants, respectively.

Conclusions: HSV529 vaccine was safe and elicited neutralizing antibody and modest CD4+ T-cell responses in HSV-seronegative vaccinees.

Clinical trials registration: NCT01915212.

Keywords: HSV2; Herpes simplex; genital herpes; vaccine.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Double-Blind Method
  • Female
  • Herpes Genitalis / immunology
  • Herpes Genitalis / prevention & control*
  • Herpes Simplex / immunology
  • Herpes Simplex / prevention & control*
  • Herpesvirus 1, Human / immunology
  • Herpesvirus 2, Human / immunology*
  • Humans
  • Male
  • Neutralization Tests
  • Vaccination*
  • Viral Vaccines / administration & dosage*
  • Viral Vaccines / immunology*
  • Viral Vaccines / therapeutic use
  • Young Adult


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Viral Vaccines

Associated data

  • ClinicalTrials.gov/NCT01915212