Broad and potent neutralization of HIV-1 by a gp41-specific human antibody
By Jinghe Huang, G. Ofek, Leo Laub, M. Louder, N. Doria-Rose, N. Longo, H. Imamichi, R. Bailer, B. Chakrabarti, S. Sharma and 10 more. Nature, 2012
896 citations recorded by the source corpus.
Characterization of human monoclonal antibodies is providing considerable insight into mechanisms of broad HIV-1 neutralization. Here we report an HIV-1 gp41 membrane-proximal external region (MPER)-specific antibody, named 10E8, which neutralizes ∼98% of tested viruses. An analysis of sera from 78 healthy HIV-1-infected donors demonstrated that 27% contained MPER-specific antibodies and 8% contained 10E8-like specificities. In contrast to other neutralizing MPER antibodies, 10E8 did not bind phospholipids, was not autoreactive, and bound cell-surface envelope. The structure of 10E8 in complex with the complete MPER revealed a site of vulnerability comprising a narrow stretch of highly conserved gp41-hydrophobic residues and a critical arginine or lysine just before the transmembrane region. Analysis of resistant HIV-1 variants confirmed the importance of these residues for neutralization. The highly conserved MPER is a target of potent, non-self-reactive neutralizing antibodies, suggesting that HIV-1 vaccines should aim to induce antibodies to this region of HIV-1 envelope glycoprotein.
Subfields: Hepatology, Infectious Diseases, Virology
View Paper: https://www.semanticscholar.org/paper/28e5a1220bfd008863592a9ec29d5a1672d400b2
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Citations in the corpus
- Therapeutic Efficacy of Potent Neutralizing HIV-1-Specific Monoclonal Antibodies in SHIV-Infected Rhesus Monkeys (2013, positive): “A series of broad and potent HIV-1 Env-specific mAbs have recently been isolated 1,2 and have been shown to target the CD4 binding site 3–7 , the V1/V2 loops 8,9 , the V3/V4 loops and N332 glycans 10–13 , and the membrane proximal external region (MPER) 14 .”
- Human Circulating PD-1+CXCR3−CXCR5+ Memory Tfh Cells Are Highly Functional and Correlate with Broadly Neutralizing HIV Antibody Responses (2013, neutral): “HIV bnAbs that can neutralize 70% or more of globally circulating HIV strains (Huang et al., 2012; Scheid et al., 2011; Walker et al., 2011; 2009) and can prevent infection in passive-transfer experiments using non-human primates (Moldt et al.”
- IDEPI: Rapid Prediction of HIV-1 Antibody Epitopes and Other Phenotypic Features from Sequence Data Using a Flexible Machine Learning Platform (2014, background): “10E8 is a broadly neutralizing antibody that targets the MPER region [64] and shows unusual potency versus the reference panel viruses.”
- Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles (2016, neutral): “4b, right), suggesting that steric hindrance may have a significant impact on 10E8, which selects for a conformational epitope extending beyond the 4E10-binding site 16 .”
- Crystal structure of a soluble cleaved HIV-1 envelope trimer (2013, background): “The gp41 HR2 may continue to extend in the same orientation as it enters the MPER, or could change direction near residue 664 (53, 54) so that the MPER could align parallel to the trimer axis.”