dc.contributor.author | Hemashettar, Girish | |
dc.contributor.author | Wang, Wendy | |
dc.contributor.author | Novembre, Francis J. | |
dc.contributor.author | Villinger, Francois | |
dc.contributor.author | Ibegbu, Chris | |
dc.contributor.author | Patel, Kalpana | |
dc.contributor.author | Corti, Davide | |
dc.contributor.author | Agatic, Gloria | |
dc.contributor.author | Vanzetta, Fabrizia | |
dc.contributor.author | Bianchi, Siro | |
dc.contributor.author | Heeney, Jonathan L. | |
dc.contributor.author | Sallusto, Federica | |
dc.contributor.author | Lanzavecchia, Antonio | |
dc.contributor.author | Watkins, Jennifer D | |
dc.contributor.author | Siddappa, Nagadenahalli B. | |
dc.contributor.author | Lakhashe, Samir | |
dc.contributor.author | Humbert, Michael | |
dc.contributor.author | Sholukh, Anton M | |
dc.contributor.author | Wong, Yin Ling | |
dc.contributor.author | Yoon, John C. | |
dc.contributor.author | Ruprecht, Ruth Margrit | |
dc.date.accessioned | 2011-12-24T17:48:27Z | |
dc.date.issued | 2011 | |
dc.identifier.citation | Watkins, 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. | en_US |
dc.identifier.issn | 1932-6203 | en_US |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:5978687 | |
dc.description.abstract | 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. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Public Library of Science | en_US |
dc.relation.isversionof | doi:10.1371/journal.pone.0018207 | en_US |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069056/pdf/ | en_US |
dash.license | LAA | |
dc.subject | animal models of infection | en_US |
dc.subject | immunodeficiency viruses | en_US |
dc.subject | humoral immunity | en_US |
dc.subject | immunoglobulins | en_US |
dc.subject | virology | en_US |
dc.subject | immunology | en_US |
dc.subject | microbiology | en_US |
dc.title | 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 | en_US |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en_US |
dc.relation.journal | PLoS ONE | en_US |
dash.depositing.author | Siddappa, Nagadenahalli B. | |
dc.date.available | 2011-12-24T17:48:27Z | |
dash.affiliation.other | HMS^Medicine-Brigham and Women's Hospital | en_US |
dash.affiliation.other | HMS^Medicine-Brigham and Women's Hospital | en_US |
dash.affiliation.other | HMS^Medicine-Brigham and Women's Hospital | en_US |
dash.affiliation.other | HMS^Medicine-Brigham and Women's Hospital | en_US |
dc.identifier.doi | 10.1371/journal.pone.0018207 | * |
dash.authorsordered | false | |
dash.contributor.affiliated | Watkins, Jennifer D. | |
dash.contributor.affiliated | Lakhashe, Samir | |
dash.contributor.affiliated | Sholukh, Anton M. | |
dash.contributor.affiliated | Yoon, John C. | |
dash.contributor.affiliated | Siddappa, Nagadenahalli B. | |
dash.contributor.affiliated | Humbert, Michael | |
dash.contributor.affiliated | Ruprecht, Ruth Margrit | |