Public antibodies: convergent signatures in human humoral immunity against pathogens DOI Creative Commons
Vishal Rao, Camila H. Coelho

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

Published: April 16, 2025

ABSTRACT The human humoral immune system has evolved to recognize a vast array of pathogenic threats. This ability is primarily driven by the immense diversity antibodies generated gene rearrangement during B cell development. However, different people often produce strikingly similar when exposed same antigen—known as public antibodies. Public not only reflect system’s consistently select for optimal cells but can also serve signatures responses triggered infection and vaccination. In this Minireview, we examine compare antibody identification methods, including criteria used based on V(D)J usage similarity in complementarity-determining region three sequences, explore molecular features elicited against common pathogens, viruses, protozoa, bacteria. Finally, discuss evolutionary significance potential applications informing design germline-targeting vaccines, predicting escape mutations emerging providing insights into process affinity maturation. ongoing discovery response pathogens holds improve pandemic preparedness, accelerate vaccine efforts, deepen our understanding biology.

Language: Английский

Phenotypic evolution of SARS-CoV-2 spike during the COVID-19 pandemic DOI Creative Commons
Wilhelm Furnon, Vanessa M. Cowton, Giuditta De Lorenzo

et al.

Nature Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Abstract SARS-CoV-2 variants are mainly defined by mutations in their spike. It is therefore critical to understand how the evolutionary trajectories of spike affect virus phenotypes. So far, it has been challenging comprehensively compare many spikes that emerged during pandemic a single experimental platform. Here we generated panel recombinant viruses carrying different proteins from 27 circulating between 2020 and 2024 same genomic background. We then assessed several phenotypic traits both vitro vivo. found distinct among before after emergence Omicron variants. Spike post-Omicron maintained enhanced tropism for nasal epithelium large airways but displayed, over time, typical pre-Omicron Hence, with features pre- may continue emerge future.

Language: Английский

Citations

3
Structural Immunology of SARS‐CoV‐2 DOI Creative Commons
Meng Yuan, Ian A. Wilson

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

Citations

4
The Compensatory Effect of S375F on S371F Is Vital for Maintaining the Infectivity of SARS‐CoV‐2 Omicron Variants DOI Creative Commons
Shuo Liu, Pan Liu,

Qiong Lu

et al.

Journal of Medical Virology, Journal Year: 2025, Volume and Issue: 97(3)

Published: March 1, 2025

The emergence of Omicron variants dramatically changed the transmission rate and infection characteristics compared to previously prevalent strains, primarily due spike protein mutations. However, impact individual mutations remained unclear. Here, we used virus-like particle (VLP) pseudotyped investigate functional contributions by 12 common in protein. We found that S371F mutation receptor binding domain (RBD) led a 5- 10-fold decrease ACE2 utilization efficiency viral infectivity, respectively, accompanied 11-fold reduction neutralization sensitivity monoclonal antibodies. S375F RBD had compensatory effect, rescuing infectivity variant. Based on molecular dynamics simulations, proposed "tug war" model explain this compensation phenomenon. These results provide comprehensive dynamic perspective evolution important pandemic virus.

Language: Английский

Citations

0
Public antibodies: convergent signatures in human humoral immunity against pathogens DOI Creative Commons
Vishal Rao, Camila H. Coelho

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

Published: April 16, 2025

ABSTRACT The human humoral immune system has evolved to recognize a vast array of pathogenic threats. This ability is primarily driven by the immense diversity antibodies generated gene rearrangement during B cell development. However, different people often produce strikingly similar when exposed same antigen—known as public antibodies. Public not only reflect system’s consistently select for optimal cells but can also serve signatures responses triggered infection and vaccination. In this Minireview, we examine compare antibody identification methods, including criteria used based on V(D)J usage similarity in complementarity-determining region three sequences, explore molecular features elicited against common pathogens, viruses, protozoa, bacteria. Finally, discuss evolutionary significance potential applications informing design germline-targeting vaccines, predicting escape mutations emerging providing insights into process affinity maturation. ongoing discovery response pathogens holds improve pandemic preparedness, accelerate vaccine efforts, deepen our understanding biology.

Language: Английский

Citations

0