{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T17:48:24Z","timestamp":1782409704433,"version":"3.54.5"},"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100032339","name":"BioNTech, SE","doi-asserted-by":"crossref","award":["Not applicable"],"award-info":[{"award-number":["Not applicable"]}],"id":[{"id":"10.13039\/100032339","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["RO1AI139618"],"award-info":[{"award-number":["RO1AI139618"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Our vaccine candidate for genital herpes includes three immunogens involved in virus entry and immune evasion. HSV-2 glycoprotein C (gC2) is one of the immune evasion molecules that inhibits complement activation by binding C3b, and is the focus of this manuscript. Mice were immunized with 0.25, 0.5, 1, 10, or 30 \u00b5g of gC2 lipid\u00a0nano particle\u00a0(LNP)-encapsulated nucleoside-modified mRNA and challenged intravaginally with HSV-2. The gC2 mRNA-LNP, even at the lowest dose, was highly protective as a single immunogen. We measured antibody responses to six gC2 epitopes. Both neutralizing and C3b binding epitopes on gC2 were targeted. We passively immunized mice with monoclonal antibodies (mAbs) to gC2 and determined that the mAbs that enhance complement activation by blocking C3b binding were protective, while the mAb that neutralizes the virus, but does not block C3b binding, failed to protect. These results highlight the importance of a vaccine immunogen that induces antibodies that block the ability of gC to inhibit complement activation.<\/jats:p>","DOI":"10.1371\/journal.ppat.1014337","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T17:23:17Z","timestamp":1782408197000},"page":"e1014337","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["HSV-2 gC2 mRNA immunization in mice protects by producing antibodies that bind immune evasion epitopes"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5540-2459","authenticated-orcid":true,"given":"Lauren M.","family":"Hook","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina M.","family":"Cairns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sita","family":"Awasthi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin P.","family":"Egan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manaswini","family":"Gopalakrishnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zauraiz","family":"Syeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Pardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Bergstrom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary H.","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harvey M.","family":"Friedman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"issue":"1","key":"ppat.1014337.ref001","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1086\/338231","article-title":"Risk of human immunodeficiency virus infection in herpes simplex virus type 2-seropositive persons: a meta-analysis","volume":"185","author":"A Wald","year":"2002","journal-title":"J Infect Dis"},{"issue":"6","key":"ppat.1014337.ref002","doi-asserted-by":"crossref","first-page":"958","DOI":"10.7326\/0003-4819-98-6-958","article-title":"Genital herpes simplex virus infections: clinical manifestations, course, and complications","volume":"98","author":"L Corey","year":"1983","journal-title":"Ann Intern Med"},{"issue":"1","key":"ppat.1014337.ref003","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJMoa035144","article-title":"Once-daily valacyclovir to reduce the risk of transmission of genital herpes","volume":"350","author":"L Corey","year":"2004","journal-title":"N Engl J Med"},{"issue":"14","key":"ppat.1014337.ref004","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1056\/NEJMoa1003509","article-title":"Oral acyclovir suppression and neurodevelopment after neonatal herpes","volume":"365","author":"DW Kimberlin","year":"2011","journal-title":"N Engl J Med"},{"issue":"4","key":"ppat.1014337.ref005","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1001\/jama.282.4.331","article-title":"Recombinant glycoprotein vaccine for the prevention of genital HSV-2 infection: two randomized controlled trials. 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