Structural Immunology of SARS‐CoV‐2

Immunological Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 27, 2024

The SARS-CoV-2 spike (S) protein has undergone significant evolution, enhancing both receptor binding and immune evasion. In this review, we summarize ongoing efforts to develop antibodies targeting various epitopes of the S protein, focusing on their neutralization potency, breadth, escape mechanisms. Antibodies receptor-binding site (RBS) typically exhibit high neutralizing potency but are frequently evaded by mutations in variants. contrast, conserved regions, such as S2 stem helix fusion peptide, broader reactivity generally lower potency. However, several broadly have demonstrated exceptional efficacy against emerging variants, including latest omicron subvariants, underscoring potential vulnerable sites RBS-A RBS-D/CR3022. We also highlight public classes different protein. targeted present opportunities for germline-targeting vaccine strategies. Overall, developing escape-resistant, potent effective vaccines remains crucial combating future This review emphasizes importance identifying key utilizing antibody affinity maturation inform therapeutic design.

Language: Английский

Rapid restoration of potent neutralization activity against the latest Omicron variant JN.1 via AI rational design and antibody engineering

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(6)

Published: Feb. 5, 2025

The rapid evolution of the viral genome has led to continual generation new variants SARS-CoV-2. Developing antibody drugs with broad-spectrum and high efficiency is a long-term task. It promising but challenging develop therapeutic neutralizing antibodies (nAbs) through in vitro based on antigen–antibody binding interactions. From an early B cell repertoire, we isolated 8G3 that retains its nonregressive activity against Omicron BA.1 various other strains vitro. protected ACE2 transgenic mice from WA1/2020 virus infection without adverse clinical manifestations completely cleared load lungs. Similar most IGHV3–53 antibodies, sites largely overlap, enabling competition for RBD. By comprehensively considering free energy changes complexes, biological environment their interactions, evolutionary direction were able select 50 mutants. Among them, 11 validated by experiments showing better activities. Further, combination four mutations identified increased neutralization potency JN.1, latest mutant, approximately 1,500-fold, one improvement multiple certain extent. Together, established procedure selection potent SARS-CoV-2 activity. Our results provide reference engineering future even pandemic viruses.

Language: Английский

A distinctive IGHV3-66 SARS-CoV-2 neutralizing antibody elicited by primary infection with an Omicron variant

Structure, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский