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. (6th May 2019)

• Record Type: Journal Article
• Authors: Dropulic, Lesia K; Oestreich, Makinna C; Pietz, Harlan L; Laing, Kerry J; Hunsberger, Sally; Lumbard, Keith; Garabedian, Doreen; Turk, Siu Ping; Chen, Aiying; Hornung, Ronald L; Seshadri, Chetan; Smith, Malisa T; Hosken, Nancy A; Phogat, Sanjay; Chang, Lee-Jah; Koelle, David M; Wang, Kening; Cohen, Jeffrey I
• Is Part Of: Journal of infectious diseases. Volume 220:Number 6(2019)
• Page Start: 990
• Page End: 1000
• Publication Date: 2019-05-06
• Subjects: Herpes simplex -- HSV2 -- vaccine -- genital herpes; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiz225
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: 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. Abstract : A replication-defective herpes simplex virus type 2 (HSV2) vaccine is safe, well tolerated, and immunogenic in HSV naive and previously HSV-infected subjects.