Neutralization escape, infectivity, and membrane fusion of JN.1-derived SARS-CoV-2 SLip, FLiRT, and KP.2 variants.

CP: Microbiology FLiRT JN.1 KP.2 SARS-CoV-2 mRNA vaccination neutralizing antibodies

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
17 Jul 2024
Historique:
received: 20 05 2024
revised: 15 06 2024
accepted: 02 07 2024
medline: 18 7 2024
pubmed: 18 7 2024
entrez: 18 7 2024
Statut: aheadofprint

Résumé

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.

Identifiants

DOI: 10.1016/j.celrep.2024.114520 PMID: 39024099
pubmed: 39024099
pii: S2211-1247(24)00849-0
doi: 10.1016/j.celrep.2024.114520
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

114520

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Pei Li (P)

Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA.

Julia N Faraone (JN)

Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA; Molecular, Cellular, and Developmental Biology Program, The Ohio State University, Columbus, OH 43210, USA.

Cheng Chih Hsu (CC)

Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA.

Michelle Chamblee (M)

Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA.

Yi-Min Zheng (YM)

Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA.

Claire Carlin (C)

Department of Internal Medicine, Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH 43210, USA.

Joseph S Bednash (JS)

Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University, Columbus, OH 43210, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.

Jeffrey C Horowitz (JC)

Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University, Columbus, OH 43210, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.

Rama K Mallampalli (RK)

Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University, Columbus, OH 43210, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.

Linda J Saif (LJ)

Center for Food Animal Health, Animal Sciences Department, OARDC, College of Food, Agricultural and Environmental Sciences, The Ohio State University, Wooster, OH 44691, USA; Veterinary Preventive Medicine Department, College of Veterinary Medicine, The Ohio State University, Wooster, OH 44691, USA; Viruses and Emerging Pathogens Program, Infectious Diseases Institute, The Ohio State University, Columbus, OH 43210, USA.

Eugene M Oltz (EM)

Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210, USA; Pelotonia Institute for Immuno-Oncology, The Ohio State University, Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH, USA.

Daniel Jones (D)

Department of Pathology, The Ohio State University, Wexner Medical Center, Columbus, OH, USA.

Jianrong Li (J)

Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA.

Richard J Gumina (RJ)

Department of Internal Medicine, Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH 43210, USA; Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA; Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Wexner Medical Center, Columbus, OH 43210, USA.

Kai Xu (K)

Texas Therapeutic Institute, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.

Shan-Lu Liu (SL)

Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA; Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA; Viruses and Emerging Pathogens Program, Infectious Diseases Institute, The Ohio State University, Columbus, OH 43210, USA; Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210, USA. Electronic address: liu.6244@osu.edu.

Classifications MeSH