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
| Autor: | Kening Wang, David M. Koelle, Sally Hunsberger, Siu Ping Turk, Ronald L Hornung, Aiying Chen, Kerry J. Laing, Chetan Seshadri, Lesia K. Dropulic, Sanjay Phogat, Lee-Jah Chang, Malisa T. Smith, Jeffrey I. Cohen, Makinna C Oestreich, Doreen Garabedian, Nancy Ann Hosken, Keith Lumbard, Harlan L Pietz |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male 0301 basic medicine medicine.medical_specialty Herpesvirus 2 Human Herpesvirus 1 Human CD8-Positive T-Lymphocytes Antibodies Viral Placebo medicine.disease_cause Young Adult Major Articles and Brief Reports 03 medical and health sciences 0302 clinical medicine Double-Blind Method Neutralization Tests Internal medicine Clinical endpoint medicine Humans Immunology and Allergy 030212 general & internal medicine Neutralizing antibody Herpes Genitalis biology business.industry Vaccination Herpes Simplex Viral Vaccines Antibodies Neutralizing Confidence interval Clinical trial Titer 030104 developmental biology Infectious Diseases Herpes simplex virus biology.protein Female business |
| Zdroj: | J Infect Dis |
| ISSN: | 1537-6613 0022-1899 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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