Faculty, Staff and Student Publications
Publication Date
8-27-2024
Journal
Cell Reports
Abstract
We investigate JN.1-derived subvariants SLip, FLiRT, and KP.2 for neutralization by antibodies in vaccinated individuals, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients, or class III monoclonal antibody S309. Compared to JN.1, SLip, KP.2, and especially FLiRT exhibit increased resistance to bivalent-vaccinated and BA.2.86/JN.1-wave convalescent human sera. XBB.1.5 monovalent-vaccinated hamster sera robustly neutralize FLiRT and KP.2 but have reduced efficiency for SLip. All subvariants are resistant to S309 and show decreased infectivity, cell-cell fusion, and spike processing relative to JN.1. Modeling reveals that L455S and F456L in SLip reduce spike binding for ACE2, while R346T in FLiRT and KP.2 strengthens it. These three mutations, alongside D339H, alter key epitopes in spike, likely explaining the reduced sensitivity of these subvariants to neutralization. Our findings highlight the increased neutralization resistance of JN.1 subvariants and suggest that future vaccine formulations should consider the JN.1 spike as an immunogen, although the current XBB.1.5 monovalent vaccine could still offer adequate protection.
Keywords
SARS-CoV-2, Animals, Humans, Antibodies, Neutralizing, COVID-19, Spike Glycoprotein, Coronavirus, Cricetinae, Antibodies, Viral, Membrane Fusion, Antibodies, Monoclonal, Mutation, Chlorocebus aethiops, Angiotensin-Converting Enzyme 2, Epitopes, Vero Cells, Neutralization Tests, COVID-19 Vaccines
DOI
10.1016/j.celrep.2024.114520
PMID
39024099
PMCID
PMC11430188
PubMedCentral® Posted Date
September 2024
PubMedCentral® Full Text Version
Author MSS
Graphical Abstract
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Clinical Epidemiology Commons, COVID-19 Commons, Medical Sciences Commons, Oncology Commons
Comments
Associated Data
PMID: 39024099