Hemashettar, GirishWang, WendyNovembre, Francis J.Villinger, FrancoisIbegbu, ChrisPatel, KalpanaCorti, DavideAgatic, GloriaVanzetta, FabriziaBianchi, SiroHeeney, Jonathan L.Sallusto, FedericaLanzavecchia, AntonioWatkins, Jennifer D.Siddappa, Nagadenahalli B.Lakhashe, SamirHumbert, MichaelSholukh, Anton M.Wong, Yin LingYoon, John C.Ruprecht, Ruth Margrit2011-12-242011Watkins, Jennifer D., Nagadenahalli B. Siddappa, Samir K. Lakhashe, Michael Humbert, Anton Sholukh, Girish Hemashettar, Yin Ling Wong, et al. 2011. An anti-HIV-1 V3 loop antibody fully protects cross-clade and elicits T-cell immunity in macaques mucosally challenged with an R5 clade C SHIV. PLoS ONE 6(3): e18207.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:5978687Neutralizing antibodies have been shown to protect macaques against SHIV challenge. However, genetically diverse HIV-1 clades have evolved, and a key question left unanswered is whether neutralizing antibodies can confer cross-clade protection in vivo. The novel human monoclonal antibody HGN194 was isolated from an individual infected with an HIV-1 clade AG recombinant circulating recombinant form (CRF). HGN194 targets an epitope in the third hypervariable loop (V3) of HIV-1 gp120 and neutralizes a range of relatively neutralization-sensitive and resistant viruses. We evaluated the potential of HGN194 to protect infant rhesus monkeys against a SHIV encoding a primary CCR5-tropic HIV-1 clade C envelope. After high-dose mucosal challenge, all untreated controls became highly viremic while all HGN194-treated animals (50 mg/kg) were completely protected. When HGN194 was given at 1 mg/kg, one out of two monkeys remained aviremic, whereas the other had delayed, lower peak viremia. Interestingly, all protected monkeys given high-dose HGN194 developed Gag-specific proliferative responses of both CD4+ and CD8+ T cells. To test whether generation of the latter involved cryptic infection, we ablated CD8+ cells after HGN194 clearance. No viremia was detected in any protected monkeys, thus ruling out virus reservoirs. Thus, induction of CD8 T-cell immunity may have resulted from transient “Hit and Run” infection or cross priming via Ag-Ab-mediated cross-presentation. Together, our data identified the HGN194 epitope as protective and provide proof-of-concept that this anti-V3 loop mAb can prevent infection with sterilizing immunity after challenge with virus of a different clade, implying that V3 is a potential vaccine target.en-USanimal models of infectionimmunodeficiency viruseshumoral immunityimmunoglobulinsvirologyimmunologymicrobiologyJournal Article2011-12-2410.1371/journal.pone.0018207