Journal article

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
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    31.03.2011
Published in:
  • 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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  • English
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Medicine
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https://susi.usi.ch/usi/documents/319009
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