{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:19:52Z","timestamp":1785406792426,"version":"3.56.0"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000200","name":"U.S. Agency for International Development","doi-asserted-by":"publisher","award":["Cooperative Agreement #7200AA22CA00002"],"award-info":[{"award-number":["Cooperative Agreement #7200AA22CA00002"]}],"id":[{"id":"10.13039\/100000200","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,6,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Griffithsin (GRFT) is an antiviral lectin that blocks human immunodeficiency virus (HIV) entry. When combined with carrageenan (CG), GRFT has strong activity against herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV). We conducted a preclinical evaluation of a high-dose vaginal fast-dissolving insert (FDI) containing 3 mg GRFT\u2014equivalent to 3\u00d7 the clinical dose\u2014and compared it with a 1 mg formulation. Studies included FDI disintegration (macaques, rabbits); GRFT pharmacokinetics, pharmacodynamics, and inflammatory response (macaques); toxicity (rats); and immunogenicity (macaques, rats). Disintegration times varied between species, emphasizing the importance of evaluating this parameter in humans. In macaques, cervico-vaginal lavage (CVL) GRFT concentrations exceeded levels associated with\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      efficacy 12 h after administration of the 3 mg GRFT\/CG FDI. Potent anti-HIV1\n                      <jats:sub>BaL<\/jats:sub>\n                      activity was detected in CVLs collected 24 h following the 3 mg dose and 12 h after the 1 mg dose. CVLs inhibited HSV-2 at 4 h and HPV at 12 h after both GRFT doses. GRFT\/CG FDIs caused no inflammatory response and did not alter vaginal pH. In rats, repeated daily dosing at up to 10\u00d7 the clinical dose revealed no safety concerns. Although anti-drug antibodies (ADAs) developed in macaques and rats, systemic GRFT was undetectable, suggesting that ADAs are unlikely to alter pharmacokinetics. Overall, the CVL GRFT concentrations and anti-HIV activity following administration of 3 mg GRFT\/CG FDIs suggest a longer protection window\u2014at least 12 h\u2014against HIV-1 compared with the 1 mg FDI, and both formulations demonstrate activity against HSV-2 and HPV. These findings support continued GRFT\/CG FDI development.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>There is an undeniable need to develop multipurpose prevention products that simultaneously protect against human immunodeficiency virus (HIV) and other sexually transmitted pathogens. To that end, we conducted a preclinical evaluation of a carrageenan-based fast-dissolving vaginal insert containing 3 mg of anti-viral lectin Griffithsin\u2014equivalent to 3\u00d7 clinical dose\u2014and compared it with a 1 mg insert. Both formulations were safe and demonstrated potent anti-HIV, herpes simplex virus type 2 (HSV-2), and human papillomavirus (HPV) activity. Our data suggest that a 3\u00d7 clinical dose Griffithsin formulation may afford an extended window of protection against HIV compared to the 1\u00d7 dose formulation. These data support further development and clinical testing of high-dose Griffithsin carrageenan fast-dissolving vaginal insert.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01966-25","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T09:58:55Z","timestamp":1776679135000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical evaluation of high-dose Griffithsin carrageenan fast-dissolving insert for HIV, HSV-2, and HPV prevention"],"prefix":"10.1128","volume":"14","author":[{"given":"J. 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