Centre d'Immunology Marseille-Luminy (CIML), Inserm
Host : P. Martineau (IRCM)
We longitudinally tracked the B-cell repertoires of 10 individuals after SARS-CoV-2 infection and repeated vaccinations. We reconstructed in vitro the naive sequences of a curated selection of 10,000 clonal lineages and measured their affinity for the spike protein binding domain of SARS-CoV-2. Our findings reveal that while the overall properties of the repertoire, including diversity, expansion, and V-gene usage, remained stable and similar to healthy individuals, the 'binder' lineages, whose naive sequence is capable of antigen binding, expanded more and had higher mutation rates. Their evolutionary patterns also differed markedly from non-binders. Among the binders, the high-affinity binder lineages showed the most activity and diversified more across the time points. We also demonstrate that lineages with identical naive sequences in different individuals evolve in similar ways. This comprehensive dataset of antibody-spike interactions in a real-world setting provides insights into detecting reacting clones within a repertoire and helps us understand how the functional diversity of the naive repertoire shapes the adaptive immune response to vaccination.