AUTHOR=Hodgson David , Liu Yi , Carolan Louise , Mahanty Siddhartha , Subbarao Kanta , Sullivan Sheena G. , Fox Annette , Kucharski Adam 

TITLE=Memory B cell proliferation drives differences in neutralising responses between ChAdOx1 and BNT162b2 SARS-CoV-2 vaccines

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1487066

DOI=10.3389/fimmu.2025.1487066

ISSN=1664-3224

ABSTRACT=IntroductionVaccination against COVID-19 has been pivotal in reducing the global burden of the disease. However, Phase III trial results and observational studies underscore differences in efficacy across vaccine technologies and dosing regimens. Notably, mRNA vaccines have exhibited superior effectiveness compared to Adenovirus (AdV) vaccines, especially with extended dosing intervals. MethodsUsing in-host mechanistic modelling, this study elucidates these variations and unravels the biological mechanisms shaping the immune responses at the cellular level. We used data on the change in memory B cells, plasmablasts, and antibody titres after the second dose of a COVID-19 vaccine for Australian healthcare workers. Alongside this dataset, we constructed a kinetic model of humoral immunity which jointly captured the dynamics of multiple immune markers, and integrated hierarchical effects into this kinetics model, including age, dosing schedule, and vaccine type.ResultsOur analysis estimated that mRNA vaccines induced 2.1 times higher memory B cell proliferation than AdV vaccines after adjusting for age, interval between doses and priming dose. Additionally, extending the duration between the second vaccine dose and priming dose beyond 28 days boosted neutralising antibody production per plasmablast concentration by 30%. We also found that antibody responses after the second dose were more persistent when mRNA vaccines were used over AdV vaccines and for longer dosing regimens. DiscussionReconstructing in-host kinetics in response to vaccination could help optimise vaccine dosing regimens, improve vaccine efficacy in different population groups, and inform the design of future vaccines for enhanced protection against emerging pathogens.