Efficient recall of SARS‐CoV‐2 variant‐reactive B cells and T responses in the elderly upon heterologous mRNA vaccines as boosters

Waning antibody levels against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of variants of concern highlight the need for booster vaccinations. This is particularly important for the elderly population, who are at a higher risk of developing severe coronavirus disease 2019 (COVID-19) disease. While studies have shown increased antibody responses following booster vaccination, understanding the changes in T and B cell compartments induced by a third vaccine dose remains limited. We analyzed the humoral and cellular responses in subjects who received either a homologous messenger RNA(mRNA) booster vaccine (BNT162b2 + BNT162b2 + BNT162b2; ''BBB") or a heterologous mRNA booster vaccine (BNT162b2 + BNT162b2 + mRNA-1273; ''BBM") at Day 0 (prebooster), Day 7, and Day 28 (postbooster). Compared with BBB, elderly individuals (≥60 years old) who received the BBM vaccination regimen display higher levels of neutralizing antibodies against the Wuhan and Delta strains along with a higher boost in immunoglobulin G memory B cells, particularly against the Omicron variant. Circulating T helper type 1(Th1), Th2, Th17, and T follicular helper responses were also increased in elderly individuals given the BBM regimen. While mRNA vaccines increase antibody, T cell, and B cell responses against SARS-CoV-2 1 month after receiving the third dose booster, the efficacy of the booster vaccine strategies may vary depending on age group and regimen combination. Agency for Science, Technology and Research (A*STAR) National Medical Research Council (NMRC) Submitted/Accepted version This study was supported by Biomedical Research Council, A*CRUSE (Vaccine monitoring project), A*ccelerate GAP‐funded project (ACCL/19‐GAP064‐R20H‐H) from Agency of Science, Technology and Research (A*STAR), Singapore National Medical Research Council COVID‐19 Research Fund (COVID19RF‐001; COVID19RF‐007; COVID19RF‐0008; COVID19RF‐060; and OFLCG19May‐0034), U.S. Food and Drug Administration (#75F40120C00085), and A*STAR COVID‐19 Research funding (H/20/04/g1/006).