Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32004464.
- Also identified by DOI 10.1016/j.cell.2020.01.010 and PMC identifier 7042716.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 clinical applications. Here we describe 1-18, a new V<sub>H</sub>1-46-encoded CD4 binding site (CD4bs) bNAb with outstanding breadth (97%) and potency (GeoMean IC<sub>50</sub> = 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<sub>SOSIP.664</sub> 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.
Medical subject headings
- Broadly Neutralizing Antibodies
- HIV Antibodies
- HIV Infections
- HIV-1
- env Gene Products, Human Immunodeficiency Virus