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Variant-specific spike conformational dynamics shape memory B cell selection during recall
Immune imprinting influences antibody responses. This study shows that the spike protein's shape, not just its sequence, can guide memory B cell recall for better vaccine protection.
Area of Science:
- Immunology
- Virology
- Structural Biology
Background:
- Immune imprinting significantly impacts antibody responses to viral infections and vaccinations.
- Current vaccine strategies often overlook the structural context of antigen recognition, focusing mainly on sequence and mutations.
Purpose of the Study:
- To investigate whether variant-specific conformational dynamics of antigens can influence memory B cell (MBC) recruitment and protective antibody responses.
- To demonstrate that antigen structure can be a factor in directing immune responses during boost immunizations.
Main Methods:
- Longitudinal analysis of memory B cell responses in boosted individuals from the COVIBOOST clinical trial.
- Functional characterization of MBC-derived monoclonal antibodies.
- Repertoire analysis, epitope mapping, and in silico structural modeling of epitope accessibility.
Main Results:
- The adjuvanted B.1.351 spike vaccine preferentially recalled MBCs targeting exposed receptor-binding domain (RBD) neutralizing epitopes.
- This preferential recruitment is linked to the more restricted conformational dynamics of the B.1.351 spike compared to the ancestral Hu-1 spike.
- Restricted dynamics of B.1.351 spike led to increased masking of cryptic RBD epitopes.
Conclusions:
- Antigen conformational dynamics can impact MBC recruitment and protective antibody responses, independent of epitope conservation.
- Leveraging antigen conformational dynamics offers a strategy to redirect pre-existing immunity toward neutralizing epitopes during boost immunization.
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