Lesia K Dropulic1, Makinna C Oestreich1, Harlan L Pietz1, Kerry J Laing2, Sally Hunsberger3, Keith Lumbard4, Doreen Garabedian4, Siu Ping Turk1, Aiying Chen5, Ronald L Hornung4, Chetan Seshadri2, Malisa T Smith2, Nancy A Hosken2, Sanjay Phogat6, Lee-Jah Chang7, David M Koelle2,8,9,10,11, Kening Wang1, Jeffrey I Cohen1. 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 receivedvaccine 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. Published by Oxford University Press for the Infectious Diseases Society of America 2019.
RCT Entities:
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. Published by Oxford University Press for the Infectious Diseases Society of America 2019.
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