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

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.

Author information

1
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda.
2
Department of Medicine, School of Medicine, University of Washington.
3
Biostatistics Research Branch, NIAID, NIH, Rockville.
4
Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, sponsored by the National Cancer Institute, NIH, Frederick, Maryland.
5
Global Biostatistics and Programming, Pennsylvania.
6
New Vaccines Portfolio Strategy and Execution, Pennsylvania.
7
Global Clinical Sciences, Sanofi Pasteur, Swiftwater, Pennsylvania.
8
Department of Laboratory Medicine, School of Medicine, University of Washington.
9
Department of Global Health, School of Medicine, University of Washington.
10
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Washington.
11
Benaroya Research Institute, Seattle, Washington.

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.

KEYWORDS:

HSV2; Herpes simplex; genital herpes; vaccine

PMID:
31058977
PMCID:
PMC6688060
[Available on 2020-08-09]
DOI:
10.1093/infdis/jiz225

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