Watkins, Jennifer D. Siddappa, Nagadenahalli B. Lakhashe, Samir K. Humbert, Michael Sholukh, Anton Hemashettar, Girish Wong, Yin Ling Yoon, John K. Wang, Wendy Novembre, Francis J. Villinger, Francois Ibegbu, Chris Patel, Kalpana Corti, Davide Agatic, Gloria Vanzetta, Fabrizio Bianchi, Siro Heeney, Jonathan L. Sallusto, Federica Lanzavecchia, Antonio Ruprecht, Ruth M. 2011-03-31 Neutralizing 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. application/pdf https://susi.usi.ch/global/documents/319009 https://localhost:5000/ark:/12658/srd1319009 https://susi.usi.ch/documents/319009/files/watkins_pone_2011.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0018207 info:eu-repo/semantics/altIdentifier/ark/12658/srd1319009 info:eu-repo/semantics/openAccess CC BY Plos one. - 2011, vol. 6, no. 3, p. e18207 info:eu-repo/classification/udc/61 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 http://purl.org/coar/resource_type/c_6501