A retrospective analysis of BNT162b2 and mRNA-1273 SARS-CoV-2 mRNA vaccination history and its effects on humoral and cellular immunity in older adults: did vaccine type matter?

COVID-19 vaccines are effective in preventing infection, hospitalization and death. Yet, despite high vaccination rates, older adults remain at increased risk of COVID-19. Studying vaccination responses in vulnerable older adults will help identify why they remain at higher risk of infection, inform equitable decisions about the design and use of current COVID-19 vaccines, as well as identify strategies to optimize immune protection and future vaccine development. We hypothesized that mRNA vaccine type may affect immune protection. A longitudinal analysis of immune protection after vaccination was conducted in 750 residents of 26 long-term care and retirement homes in the observational cohort COVID in Long-Term Care Study in Ontario, Canada. Antibody and cellular immune responses were assessed in blood samples collected between April 2021 and July 2023 every 3 months after vaccinations with primary (two-dose), third and fourth monovalent (ancestral SARS-CoV-2), fifth bivalent (ancestral and Omicron BA.1 SARS-CoV-2) and sixth bivalent (ancestral and Omicron BA.4/5 SARS-CoV-2) vaccines. Measurements included total quantities of circulating antibodies and high-quality neutralizing antibodies, as well as T cell responses. Antibody and T cell immunity after monovalent and bivalent vaccinations was compared between individuals who received all mRNA-1273 (Moderna) vaccines or BNT162b2 (Pfizer) vaccines, and individuals who received mixed mRNA vaccines. Older adults often had more robust antibody and T cell responses after repeated vaccinations, but distinct effects of vaccine type were noted. Higher total antibody levels, neutralizing antibodies, and T cell responses after monovalent vaccinations, and even subsequent bivalent vaccinations, were generally observed in older adults with all mRNA-1273 vaccines compared to all BNT162b2 vaccines. Therefore, vaccination history with specific mRNA vaccines may have long-term effects on protection against COVID-19 in older adults.