HIV-1 CD4-binding site germline antibody-Env structures inform vaccine design.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36253376.
- Also identified by DOI 10.1038/s41467-022-33860-2 and PMC identifier 9576718.
- 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
BG24, a VRC01-class broadly neutralizing antibody (bNAb) against HIV-1 Env with relatively few somatic hypermutations (SHMs), represents a promising target for vaccine strategies to elicit CD4-binding site (CD4bs) bNAbs. To understand how SHMs correlate with BG24 neutralization of HIV-1, we report 4.1 Å and 3.4 Å single-particle cryo-EM structures of two inferred germline (iGL) BG24 precursors complexed with engineered Env-based immunogens lacking CD4bs N-glycans. Structures reveal critical Env contacts by BG24<sub>iGL</sub> and identify antibody light chain structural features that impede Env recognition. In addition, biochemical data and cryo-EM structures of BG24<sub>iGL</sub> variants bound to Envs with CD4bs glycans present provide insights into N-glycan accommodation, including structural modes of light chain adaptations in the presence of the N276<sub>gp120</sub> glycan. Together, these findings reveal Env regions critical for germline antibody recognition and potential sites to alter in immunogen design.
Medical subject headings
- HIV Infections
- HIV-1