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- Title
SARS-CoV-2 JN.1 variant evasion of IGHV3-53/3-66 B cell germlines.
- Authors
Paciello, Ida; Maccari, Giuseppe; Pierleoni, Giulio; Perrone, Federica; Realini, Giulia; Troisi, Marco; Anichini, Gabriele; Cusi, Maria Grazia; Rappuoli, Rino; Andreano, Emanuele
- Abstract
The severe acute respiratory syndrome coronavirus 2 variant JN.1 recently emerged as the dominant variant despite having only one amino acid change on the spike (S) protein receptor binding domain (RBD) compared with the ancestral BA.2.86, which never represented more than 5% of global variants. To define at the molecular level the JN.1 ability to spread globally, we interrogated a panel of 899 neutralizing human monoclonal antibodies. Our data show that the single leucine-455–to–serine mutation in the JN.1 spike protein RBD unleashed the global spread of JN.1, likely occurring by elimination of more than 70% of the neutralizing antibodies mediated by IGHV3-53/3-66 germlines. However, the resilience of class 3 antibodies with low neutralization potency but strong Fc functions may explain the absence of JN.1 severe disease. Editor's summary: New variants of SARS-CoV-2 continue to emerge and enable viral immune evasion. Using a panel of 899 human monoclonal neutralizing antibodies (nAbs), Paciello et al. examined antibody neutralization activity and effector functions against the recently dominant JN.1 variant. Compared with the ancestral BA.2.86 strain, around two-thirds of nAbs lost neutralization activity against JN.1, including most derived from the immunoglobulin heavy chain V gene (IGHV) 3-53 and 3-66 germlines. The remaining nAbs were only detected in individuals with a history of multiple vaccinations and Omicron breakthrough infections. Among nAbs that could bind the JN.1 spike protein, Fc functions were largely retained and primarily driven by class 3 antibodies that bind outside of the ACE2 binding region, possibly explaining the absence of JN.1 severe disease despite strong evasion of class 1/2 nAbs. —Claire Olingy
- Subjects
SARS-CoV-2; IMMUNOGLOBULIN heavy chains; IMMUNE response; SARS-CoV-2 Omicron variant; BREAKTHROUGH infections
- Publication
Science Immunology, 2024, Vol 9, Issue 98, p1
- ISSN
2470-9468
- Publication type
Article
- DOI
10.1126/sciimmunol.adp9279