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

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.

doi:10.1371/journal.pone.0018207

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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

Watkins, Jennifer D. Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America - Harvard Medical School, Boston, Massachusetts, United States of America
Siddappa, Nagadenahalli B. Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America - Harvard Medical School, Boston, Massachusetts, United States of America
Lakhashe, Samir K. Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America - Harvard Medical School, Boston, Massachusetts, United States of America
Humbert, Michael Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America - Harvard Medical School, Boston, Massachusetts, United States of America
Sholukh, Anton Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America - Harvard Medical School, Boston, Massachusetts, United States of America
Hemashettar, Girish Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America
Wong, Yin Ling Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America
Yoon, John K. Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America
Wang, Wendy Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America
Novembre, Francis J. Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America - Department of Microbiology and Immunology, Emory University, Atlanta, Georgia, United States of America
Villinger, Francois Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America - Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia, United States of America
Ibegbu, Chris Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America
Patel, Kalpana Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, United States of America
Corti, Davide Humabs SAGL, Bellinzona, Switzerland
Agatic, Gloria Humabs SAGL, Bellinzona, Switzerland
Vanzetta, Fabrizio Humabs SAGL, Bellinzona, Switzerland
Bianchi, Siro Humabs SAGL, Bellinzona, Switzerland
Heeney, Jonathan L. Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom
Sallusto, Federica Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Lanzavecchia, Antonio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Ruprecht, Ruth M. Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America - Harvard Medical School, Boston, Massachusetts, United States of America

31.03.2011

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Plos one. - 2011, vol. 6, no. 3, p. e18207

English 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.

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