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

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.