Antibody-mediated protection against SHIV challenge includes systemic clearance of distal virus

Jinyan Liu(Beth Israel Deaconess Medical Center), Khader Ghneim(Case Western Reserve University), Devin Sok(Scripps Research Institute), William J. Bosche(Leidos (United States)), Li Yuan(Leidos (United States)), Elizabeth Chipriano(Leidos (United States)), Brian Berkemeier(Leidos (United States)), Kelli Oswald(Leidos (United States)), Erica N. Borducchi(Beth Israel Deaconess Medical Center), Crystal Cabral(Beth Israel Deaconess Medical Center), Lauren Peter(Beth Israel Deaconess Medical Center), Amanda Brinkman(Beth Israel Deaconess Medical Center), Mayuri Shetty(Beth Israel Deaconess Medical Center), Jessica Jimenez(Beth Israel Deaconess Medical Center), Jade Mondesir(Beth Israel Deaconess Medical Center), Benjamin Lee(Beth Israel Deaconess Medical Center), Patricia Giglio(Beth Israel Deaconess Medical Center), Abishek Chandrashekar(Beth Israel Deaconess Medical Center), Peter Abbink(Beth Israel Deaconess Medical Center), Arnaud D. Colantonio(Harvard University), Courtney Gittens(Bioqual), Chantélle Baker(Bioqual), Wendeline Wagner(Bioqual), Mark G. Lewis(Bioqual), Wenjun Li(University of Massachusetts Chan Medical School), Rafick‐Pierre Sékaly(Case Western Reserve University), Jeffrey D. Lifson(Leidos (United States)), Dennis R. Burton(Scripps Research Institute), Dan H. Barouch(Beth Israel Deaconess Medical Center)
Science
August 19, 2016
10.1126/science.aag0491
Cited by 137Open Access
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Abstract

HIV-1-specific broadly neutralizing antibodies (bNAbs) can protect rhesus monkeys against simian-human immunodeficiency virus (SHIV) challenge. However, the site of antibody interception of virus and the mechanism of antibody-mediated protection remain unclear. We administered a fully protective dose of the bNAb PGT121 to rhesus monkeys and challenged them intravaginally with SHIV-SF162P3. In PGT121-treated animals, we detected low levels of viral RNA and viral DNA in distal tissues for seven days following challenge. Viral RNA-positive tissues showed transcriptomic changes indicative of innate immune activation, and cells from these tissues initiated infection after adoptive transfer into naïve hosts. These data demonstrate that bNAb-mediated protection against a mucosal virus challenge can involve clearance of infectious virus in distal tissues.

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