{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:55:45Z","timestamp":1792684545295,"version":"4.5.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"6","funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["HHSN261200800001E"],"award-info":[{"award-number":["HHSN261200800001E"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,8,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Herpes simplex virus 2 (HSV2) causes genital herpes in &gt;400 million persons worldwide.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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\u2212\/HSV2\u2212), those positive or negative for HSV1 and positive for HSV2 (HSV1\u00b1\/HSV2+), and those positive for HSV1 and negative for HSV2 (HSV1+\/HSV2\u2212). 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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%\u201367.6%; P = .006). Sixty-four percent of vaccinees experienced systemic reactions, compared with 53% of placebo recipients (95% CI, \u221217.9% to 40.2%; P = .44). Seventy-eight percent of HSV1\u2212\/HSV2\u2212 vaccine recipients had a \u22654-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\u2212\/HSV2\u2212, HSV1\u00b1\/HSV2+, and HSV1+\/HSV2\u2212 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>HSV529 vaccine was safe and elicited neutralizing antibody and modest CD4+ T-cell responses in HSV-seronegative vaccinees.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Clinical Trials Registration<\/jats:title>\n                  <jats:p>NCT01915212.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiz225","type":"journal-article","created":{"date-parts":[[2019,5,3]],"date-time":"2019-05-03T07:08:44Z","timestamp":1556867324000},"page":"990-1000","source":"Crossref","is-referenced-by-count":65,"title":["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"],"prefix":"10.1093","volume":"220","author":[{"given":"Lesia K","family":"Dropulic","sequence":"first","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makinna C","family":"Oestreich","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harlan L","family":"Pietz","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry J","family":"Laing","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, University of Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally","family":"Hunsberger","sequence":"additional","affiliation":[{"name":"Biostatistics Research Branch, NIAID, NIH, Rockville"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Lumbard","sequence":"additional","affiliation":[{"name":"Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, sponsored by the National Cancer Institute, NIH, Frederick, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doreen","family":"Garabedian","sequence":"additional","affiliation":[{"name":"Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, sponsored by the National Cancer Institute, NIH, Frederick, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siu Ping","family":"Turk","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiying","family":"Chen","sequence":"additional","affiliation":[{"name":"Global Biostatistics and Programming, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald L","family":"Hornung","sequence":"additional","affiliation":[{"name":"Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, sponsored by the National Cancer Institute, NIH, Frederick, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chetan","family":"Seshadri","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, University of Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malisa T","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, University of Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy A","family":"Hosken","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, University of Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Phogat","sequence":"additional","affiliation":[{"name":"New Vaccines Portfolio Strategy and Execution, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee-Jah","family":"Chang","sequence":"additional","affiliation":[{"name":"Global Clinical Sciences, Sanofi Pasteur, Swiftwater, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M","family":"Koelle","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, University of Washington"},{"name":"Department of Laboratory Medicine, School of Medicine, University of Washington"},{"name":"Department of Global Health, School of Medicine, University of Washington"},{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Washington"},{"name":"Benaroya Research Institute, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kening","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases 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