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Intern. AIDS Soc."],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>The majority of new HIV infections occur through mucosal transmission. The availability of readily applicable and accessible platforms for anti\u2010retroviral (ARV) delivery is critical for the prevention of HIV acquisition through sexual transmission in both women and men. There is a compelling need for developing new topical delivery systems that have advantages over the pills, gels and rings, which currently fail to guarantee protection against mucosal viral transmission in vulnerable populations due to lack of user compliance. The silk fibroin (SF) platform offers another option that may be better suited to individual circumstances and preferences to increase efficacy through user compliance. The objective of this study was to test safety and efficacy of SF for anti\u2010HIV drug delivery to mucosal sites and for viral prevention.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We formulated a potent HIV inhibitor Griffithsin (Grft) in a mucoadhesive silk fibroin (SF) drug delivery platform and tested the application in a non\u2010human primate model <jats:italic>in vivo<\/jats:italic> and a pre\u2010clinical human cervical and colorectal tissue explant model. Both vaginal and rectal compartments were assessed in rhesus macaques (<jats:italic>Mucaca mulatta<\/jats:italic>) that received SF (n\u00a0=\u00a04), no SF (n\u00a0=\u00a07) and SF\u2010Grft (n\u00a0=\u00a011). In this study, we evaluated the composition of local microbiota, inflammatory cytokine production, histopathological changes in the vaginal and rectal compartments and mucosal protection after <jats:italic>ex vivo<\/jats:italic> SHIV challenge.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Effective Grft release and retention in mucosal tissues from the SF\u2010Grft platform resulted in protection against HIV in human cervical and colorectal tissue as well as against SHIV challenge in both rhesus macaque vaginal and rectal tissues. Mucoadhesion of SF\u2010Grft inserts did not cause any inflammatory responses or changes in local microbiota.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We demonstrated that <jats:italic>in vivo<\/jats:italic> delivery of SF\u2010Grft in rhesus macaques fully protects against SHIV challenge <jats:italic>ex vivo<\/jats:italic> after two hours of application and is safe to use in both the vaginal and rectal compartments. Our study provides support for the development of silk fibroin as a highly promising, user\u2010friendly HIV prevention modality to address the global disparity in HIV infection.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jia2.25628","type":"journal-article","created":{"date-parts":[[2020,10,19]],"date-time":"2020-10-19T05:22:01Z","timestamp":1603084921000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Efficacy of silk fibroin biomaterial vehicle for <i>in vivo<\/i> mucosal delivery of Griffithsin and protection against HIV and SHIV infection <i>ex vivo<\/i>"],"prefix":"10.1002","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7169-8504","authenticated-orcid":false,"given":"Katti R","family":"Crakes","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology &amp; Immunology School of Medicine University of California Davis Davis CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Herrera","sequence":"additional","affiliation":[{"name":"Department of Medicine St. Mary\u2019s Campus Imperial College London United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica L","family":"Morgan","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology University of California Merced Merced CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katie","family":"Olstad","sequence":"additional","affiliation":[{"name":"California National Primate Research Center University of California Davis Davis CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann J","family":"Hessell","sequence":"additional","affiliation":[{"name":"Division of Pathobiology and Immunology Oregon National Primate Research Center Oregon Health and Sciences University Beaverton OR USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Ziprin","sequence":"additional","affiliation":[{"name":"Department of Surgery and Cancer St. Mary\u2019s Campus Imperial College London United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia J","family":"LiWang","sequence":"additional","affiliation":[{"name":"Department of Molecular Cell Biology University of California Merced Merced CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satya","family":"Dandekar","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology &amp; Immunology School of Medicine University of California Davis Davis CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,10,18]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"Advocacy CaG.UNAIDS.2019. 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