title: Broadly Neutralizing Anti-HIV Antibodies Prevent HIV Infection of Mucosal Tissue Ex Vivo.
abstract: Broadly neutralizing monoclonal antibodies (nAbs) specific for HIV are being investigated for use in HIV prevention. Due to their ability to inhibit HIV attachment to and entry into target cells, nAbs may be suitable for use as topical HIV microbicides. As such, they would present an alternative intervention for individuals who may not benefit from using antiretroviral-based products for HIV prevention. We theorize that nAbs can inhibit viral transmission through mucosal tissue, thus reducing the incidence of HIV infection. The efficacy of the PG9, PG16, VRC01, and 4E10 antibodies was evaluated in an ex vivo human model of mucosal HIV transmission. nAbs reduced HIV transmission, causing 1.5- to 2-log10 reductions in HIV replication in ectocervical tissues and ≈3-log10 reductions in HIV replication in colonic tissues over 21 days. These antibodies demonstrated greater potency in colonic tissues, with a 50-fold higher dose being required to reduce transmission in ectocervical tissues. Importantly, nAbs retained their potency and reduced viral transmission in the presence of whole semen. No changes in tissue viability or immune activation were observed in colonic or ectocervical tissue after nAb exposure. Our data suggest that topically applied nAbs are safe and effective against HIV infection of mucosal tissue and support further development of nAbs as a topical microbicide that could be used for anal as well as vaginal protection.
authors.affiliation: Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Yanille M
authors.initials: YM
authors.lastname: Scott
authors.affiliation: School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Seo Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA Magee-Womens Research Institute, Pittsburgh, Pennsylvania, USA cdezzutti@mwri.magee.edu.
authors.forename: Charlene S
authors.initials: CS
authors.lastname: Dezzutti
mesh_terms: D000287:Administration, Topical; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D016466:CHO Cells; D002584:Cervix Uteri / Q000187:drug effects / Q000821:virology*; D003106:Colon / Q000187:drug effects / Q000821:virology; D003412:Cricetulus; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission; D006801:Humans; D008297:Male; D009092:Mucous Membrane / Q000187:drug effects / Q000821:virology; D009924:Organ Culture Techniques; D012661:Semen
chemical_list: D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing