+Search query
-Structure paper
Title | Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody. |
---|---|
Journal, issue, pages | Cell, Vol. 180, Issue 3, Page 471-489.e22, Year 2020 |
Publish date | Feb 6, 2020 |
Authors | Philipp Schommers / Henning Gruell / Morgan E Abernathy / My-Kim Tran / Adam S Dingens / Harry B Gristick / Christopher O Barnes / Till Schoofs / Maike Schlotz / Kanika Vanshylla / Christoph Kreer / Daniela Weiland / Udo Holtick / Christof Scheid / Markus M Valter / Marit J van Gils / Rogier W Sanders / Jörg J Vehreschild / Oliver A Cornely / Clara Lehmann / Gerd Fätkenheuer / Michael S Seaman / Jesse D Bloom / Pamela J Bjorkman / Florian Klein / |
PubMed Abstract | Broadly neutralizing antibodies (bNAbs) represent a promising approach to prevent and treat HIV-1 infection. However, viral escape through mutation of the HIV-1 envelope glycoprotein (Env) limits ...Broadly neutralizing antibodies (bNAbs) represent a promising approach to prevent and treat HIV-1 infection. However, viral escape through mutation of the HIV-1 envelope glycoprotein (Env) limits clinical applications. Here we describe 1-18, a new V1-46-encoded CD4 binding site (CD4bs) bNAb with outstanding breadth (97%) and potency (GeoMean IC = 0.048 μg/mL). Notably, 1-18 is not susceptible to typical CD4bs escape mutations and effectively overcomes HIV-1 resistance to other CD4bs bNAbs. Moreover, mutational antigenic profiling uncovered restricted pathways of HIV-1 escape. Of most promise for therapeutic use, even 1-18 alone fully suppressed viremia in HIV-1-infected humanized mice without selecting for resistant viral variants. A 2.5-Å cryo-EM structure of a 1-18-BG505 Env complex revealed that these characteristics are likely facilitated by a heavy-chain insertion and increased inter-protomer contacts. The ability of 1-18 to effectively restrict HIV-1 escape pathways provides a new option to successfully prevent and treat HIV-1 infection. |
External links | Cell / PubMed:32004464 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.5 - 3.9 Å |
Structure data | EMDB-20739, PDB-6udj: EMDB-20740, PDB-6udk: |
Chemicals | ChemComp-NAG: ChemComp-HOH: |
Source |
|
Keywords | VIRAL PROTEIN/IMMUNE SYSTEM / HIV-1 broadly neutralizing antibody / Env / cryo-EM / bNAb / VIRAL PROTEIN-IMMUNE SYSTEM complex / Env trimer / RC1 / CD4-binding site |