Jul 2026· International Journal of Infectious Diseases· Vol 170, pp.
108954
· 0 citations· 12 references
Medicine
TL;DR
BA.3.3.2.2 preserves class 1/2 antibody epitopes, providing a mechanistic basis for cross-neutralization and suggesting a potential therapeutic window for sipavibart should BA.3.3.2.2 expand globally, pending clinical confirmation.
Abstract
The SARS-CoV-2 BA.3.2.2 sublineage has emerged globally as the dominant branch of BA.3.2 by late 2025, yet its antigenic relationship with JN.1 vaccine-induced immunity remains unclear. We evaluated neutralizing antibody responses in 25 JN.1 mRNA vaccinees against eight variants, stratified by anti-nucleocapsid antibody serostatus. Post-vaccination titers increased significantly against all variants in both N antibody-negative and -positive groups. Cross-neutralization against BA.3.2.2 was detected in both groups despite lower titers compared to JN.1. Antigenic cartography revealed that BA.3.2.2 was antigenically isolated from all JN.1-descendant variants. AZD3152/sipavibart retained potent neutralization against BA.3.2.2 but completely lost activity against all F456L-harboring JN.1-descendant variants, while VYD222/pemivibart and SA55 maintained broad activity. Retention of wild-type F456 in BA.3.2.2 preserves class 1/2 antibody epitopes, providing a mechanistic basis for cross-neutralization and suggesting a potential therapeutic window for sipavibart should BA.3.2.2 expand globally, pending clinical confirmation.
Data indicate the KP.2 mRNA vaccine generates durable, cross-reactive responses against current Omicron subvariants, however, ongoing spike evolution impacts the neutralization of emerging lineages, highlighting the need for continued viral monitoring and timely vaccine updates.
Sanjeev Kumar, Li-Lin Lai, M. Ellis et al.· Journal of Virology· 0 citations
Data on immune responses to COVID-19 vaccination in West and Central Africa remain limited, particularly across SARS-CoV-2 variants and vaccine platforms. Using the InVITE cohort in the Democratic Republic of Congo, Guinea, Liberia, and Mali, we evaluated anti-spike (anti-S) antibody binding to nine SARS-CoV-2 variants in 96 participants equally selected from pre-vaccination assay defined seropositive and seronegative groups. Participants received mRNA, adenovirus-vectored, or inactivated virus vaccines. Anti-S binding was measured before vaccination and two months after completion of the primary series using a Meso Scale Discovery 10-plex assay. Before vaccination, antibody binding was significantly higher against pre-Omicron variants (Ancestral, Alpha, Beta, and Delta) than Omicron variants in both seronegative (fold change [FC] 3.85, 99% CI 3.45–4.17) and seropositive (FC 3.57, 99% CI 3.33–3.84) participants. Seropositive individuals showed greater binding than seronegative individuals across all variants. Two months post-vaccination, mRNA vaccines elicited higher antibody binding than adenovirus-vectored or inactivated vaccines, whereas no significant differences were observed between adenovirus-vectored and inactivated vaccines. Antibody binding remained higher against pre-Omicron than Omicron variants across all vaccine platforms and serostatus groups. These findings provide rare data on variant-specific vaccine-elicited antibody binding responses in West and Central African populations with distinct demographic, epidemiologic, and immunologic background.
Trial registration: Registration ClinicalTrials.gov: NCT05096091, Registration date: 10-26-2021, Clinical trial registry:
https://clinicaltrials.gov/study/NCT05096091?term=NCT05096091rank=1#study-overview
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E. Lusamaki, Ana M. Ortega-Villa, Daouda Camara et al.· Scientific Reports· 0 citations
The observed waning of cross-neutralizing antibodies against emerging variants underscores the challenge of maintaining durable protection and supports the need for continued monitoring of antibody responses to guide evidence-based updates to COVID-19 vaccines.
Wei Wang, E. Goguet, Sabrina Lusvarghi et al.· Open Forum Infectious Diseas...· 0 citations
It is proposed that there is somatic hypermutation of existing B cell clones rather than de novo generation from naive B cells in JN.1-adapted booster vaccines and this finding indicates maturation of pre-existing, class-switched MBC rather than substantial de novo recruitment of naïve B cells.
M. Stankov, Matthias Bruhn, M. Hoffmann et al.· Nature Communications· 0 citations
It is shown that a Wuhan-lineage-based multi-antigen VLP vaccine can provide cross-protection against an antigenically divergent SARS-CoV-2 variant that is not fully explained by detectable serum neutralizing activity alone, suggesting the importance of integrated immune responses involving humoral, cellular, and local immune mechanisms.
Seung-Ji Kim, Howon Kim, Seung-Eun Son et al.· Vaccine· 0 citations
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