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To test the hypothesis that deletion of gD-2 unmasks protective antigens, we evaluated the efficacy and safety of an HSV-2 virus deleted in gD-2 and complemented allowing a single round of replication on cells expressing HSV-1 gD (\u0394gD\u2212\/+gD\u22121). Subcutaneous immunization of C57BL\/6 or BALB\/c mice with \u0394gD\u2212\/+gD1 provided 100% protection against lethal intravaginal or skin challenges and prevented latency. \u0394gD\u2212\/+gD1 elicited no disease in SCID mice, whereas 1000-fold lower doses of wild-type virus were lethal. HSV-specific antibodies were detected in serum (titer 1:800,000) following immunization and in vaginal washes after intravaginal challenge. The antibodies elicited cell-mediated cytotoxicity, but little neutralizing activity. Passive transfer of immune serum completely protected wild-type, but not Fc\u03b3-receptor or neonatal Fc-receptor knock-out mice. These studies demonstrate that non-neutralizing Fc-mediated humoral responses confer protection and support advancement of this attenuated vaccine.<\/jats:p>","DOI":"10.7554\/elife.06054","type":"journal-article","created":{"date-parts":[[2015,3,9]],"date-time":"2015-03-09T05:37:42Z","timestamp":1425879462000},"source":"Crossref","is-referenced-by-count":100,"title":["Herpes simplex type 2 virus deleted in glycoprotein D protects against vaginal, skin and neural disease"],"prefix":"10.7554","volume":"4","author":[{"given":"Christopher","family":"Petro","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, United States"},{"name":"Howard Hughes Medical Institute, Albert Einstein College of Medicine, New York, United States"},{"name":"Department of Pediatrics, Albert Einstein College of Medicine, New York, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo 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