Details

Autor(en) / Beteiligte

• 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, Fabrizia
• Bianchi, Siro
• Heeney, Jonathan L
• Sallusto, Federica
• Lanzavecchia, Antonio
• Ruprecht, Ruth M
• Sandberg, Johan

Titel

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

Ist Teil von

• PloS one, 2011-03, Vol.6 (3), p.e18207-e18207

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.