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

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.

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.

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

NCT01915212.