Ancestral SARS-CoV-2 immune imprinting persists on RBD but not NTD after sequential Omicron infections

iScience, Journal Year: 2024, Volume and Issue: 28(1), P. 111557 - 111557

Published: Dec. 9, 2024

Language: Английский

Structural and Functional Insights into the Evolution of SARS-CoV-2 KP.3.1.1 Spike Protein

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 10, 2024

Summary The JN.1-sublineage KP.3.1.1 recently emerged as the globally prevalent SARS-CoV-2 variant, demonstrating increased infectivity and antibody escape. We investigated how mutations a deletion in spike protein (S) affect ACE2 binding Mass spectrometry revealed new glycan site at residue N30 altered glycoforms neighboring N61. Cryo-EM structures showed that rearrangement of adjacent residues did not significantly change overall structure, up-down ratio receptor-binding domains (RBDs), or binding. Furthermore, S structure with hACE2 further confirmed an epistatic effect between F456L Q493E on Our analysis shows variants after late 2023 are now incorporating reversions to found other sarbecoviruses, including glycan, Q493E, others. Overall, these results inform structural functional consequences mutations, current evolutionary trajectory, immune evasion.

Language: Английский

Immunologic and Biophysical Features of the BNT162b2 JN.1- and KP.2-Adapted COVID-19 Vaccines

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 6, 2024

ABSTRACT Vaccines remain a vital public health tool to reduce the burden of COVID-19. COVID-19 vaccines that are more closely matched circulating SARS-CoV-2 lineages elicit potent and relevant immune responses translate improved real-world vaccine effectiveness. The rise in prevalence Omicron JN.1 lineage, subsequent derivative sublineages such as KP.2 KP.3, coincided with reduced neutralizing activity effectiveness XBB.1.5-adapted vaccines. Here, we characterized biophysical immunologic attributes BNT162b2 JN.1- KP.2-adapted mRNA vaccine-encoded spike (S) protein immunogens. Biophysical interrogations S revealed structural consequences hallmark amino acid substitutions potential molecular mechanism escape employed by KP.2. candidates were evaluated for their immunogenicity when administered fourth or fifth doses BNT162b2-experienced mice primary series naïve mice. In both vaccine-experienced settings, conferred over XBB.1.5 against broad panel emerging sublineages, including predominant KP.3.1.1 XEC lineages. Antigenic mapping indicated greater antigenic overlap currently compared an vaccine. CD4 + CD8 T cell generally conserved across all three Together, data support selection 2024-25 formula. ONE-SENTENCE SUMMARY encoding prefusion proteins similar preclinical antibody sublineage pseudoviruses than those elicited past iterations licensed vaccines, thus demonstrating importance annual strain changes

Language: Английский