Scientific article
OA Policy
English

mRNA prime-boost vaccination promotes clonal continuity in germinal center reactions and broadens SARS-CoV-2 variant coverage

Published inMolecular therapy, vol. 33, no. 11, p. 5453-5469
Publication date2025-11-05
First online date2025-08-08
Abstract

mRNA- and adenovirus-based (rAd) SARS-CoV-2 vaccines have been widely used in various homologous and heterologous prime-boost combinations. It remains unknown, however, which vaccination regimens effectively promote B cell clonal continuity (i.e., the participation of individual B cell clones in durable GC reactions to prime and subsequent boost). Here, we characterize SARS-CoV-2-specific GC B cell dynamics in vaccinated mice. While rAd/mRNA prime-boost elicited SARS-CoV-2-neutralizing antibody (nAb) titers equivalent to those induced by mRNA/mRNA, the latter provided broader nAb coverage of variants of concern. B cell fate-mapping experiments revealed that mRNA/mRNA afforded higher clonal continuity between primary and secondary GC reactions than rAd/mRNA, which was associated with similarly sized but more durable GC responses upon mRNA prime. Homologous rAd/rAd prime-boost resulted in vector backbone-biased antibody responses and limited clonal continuity of SARS-CoV-2-specific B cells. Our study suggests that high clonal continuity as observed during mRNA homologous prime-boost is key for vaccination regimens against rapidly evolving pathogens.

Keywords
  • SARS-CoV-2
  • Adenovirus vector
  • Clonal selection
  • Germinal centers
  • MRNA vaccines
  • Neutralizing antibodies
  • Prime-boost immunization
  • Vaccination
  • Variant coverage
  • Animals
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / genetics
  • Mice
  • COVID-19 / immunology
  • COVID-19 / prevention & control
  • COVID-19 / virology
  • Antibodies, Neutralizing / immunology
  • COVID-19 Vaccines / immunology
  • COVID-19 Vaccines / administration & dosage
  • Germinal Center / immunology
  • B-Lymphocytes / immunology
  • Antibodies, Viral / immunology
  • Vaccination / methods
  • Immunization, Secondary
  • Humans
  • RNA, Messenger / immunology
  • RNA, Messenger / genetics
  • Female
  • Adenoviridae / genetics
Funding
Citation (ISO format)
CIANCAGLINI, Matias et al. mRNA prime-boost vaccination promotes clonal continuity in germinal center reactions and broadens SARS-CoV-2 variant coverage. In: Molecular therapy, 2025, vol. 33, n° 11, p. 5453–5469. doi: 10.1016/j.ymthe.2025.08.008
Main files (1)
Article (Published version)
Identifiers
Journal ISSN1525-0016
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34downloads

Technical informations

Creation09/12/2025 09:37:19
First validation07/01/2026 15:44:02
Update07/01/2026 15:44:02
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