Similar memory B and T cell responses in recipients of two different 2023 COVID-19 mRNA vaccine formulations with a restricted SARS-CoV-2 BA.2.86-specific MBC response

Background: We report a vaccine study on memory B/T cell responses after receipt of one of two different 2023 COVID-19 mRNA vaccine formulations.

Memory B/T cell responses over time to the SARS-CoV-2 strain Wuhan-Hu-1, Omicron subvariants BA.4/BA.5, XBB.1.5, and the mutated SARS-CoV-2 BA.2.86/Pirola variant (a predecessor of JN.1 and the KP.2 lineage/FLiRT in the 2024-2025 vaccine) were assessed.

Methods: The previously primed/immunized study subjects (n=50) received the 2023 bivalent ancestral strain/BA.4/BA.5 mRNA vaccine (Group A, n=15) or the monovalent XBB.1.5 mRNA vaccine (Group B, n=35). Blood was collected at baseline, 1 Month, 6 Months, and 12 Months post-vaccination for assessment of memory B cell (MBC) frequencies to different RBD and S antigens (memory B cell Elispot) or CD4⁺ T cell responses (IL-21/Tfh, IFNγ, and IL-2 by Fluorospot). Analyses were performed using the Wilcoxon Rank Sum or Signed Rank Tests.

Results: We found no significant differences in the antigen-specific MBC frequencies between Group A subjects and Group B subjects at any timepoints, except for the results at 6 months (higher MBC responses to all antigens in Group A subjects, p˂0.02).

We observed higher Wuhan-Hu-1 RBD- or S-specific MBC responses compared to all variant-specific MBC responses at all timepoints (p˂0.01), consistent with the “original antigenic sin” experience.

Importantly, we observed a largely reduced MBC response to the SARS-CoV-2 BA.2.86 (RBD, whole S protein) compared to all other MBC responses at all study timepoints (p≤0.01). At Month 1, the BA.2.86 RBD-specific MBC response was 3 to 4.8-fold lower compared to other RBD-specific MBC responses (p˂2E^-06). Limited difference between variant-specific CD4⁺ T cell responses was found.

Conclusion: The RBD and Spike-specific MBC responses to two different vaccine formulations demonstrated laboratory evidence of original antigenic sin. The largely restricted BA.2.86-specific MBC response suggested immune evasion and increased susceptibility to its arising subvariants.