SARS-CoV-2 infection and vaccination trigger long-lived B and CD4+ T lymphocytes: implications for booster strategies

Background: Immunization against SARS-CoV-2, the causative agent of coronavirus disease-19 (COVID-19) occurs via natural infection or vaccination. However, it is currently unknown how long infection- or vaccination-induced immunological memory will last. Methods: We performed a longitudinal evaluation of immunological memory to SARS-CoV-2 up to one year post infection and following mRNA vaccination in naïve and COVID-19 recovered individuals. Results: We found that memory cells are still detectable 8 months after vaccination, while antibody levels decline significantly especially in naïve subjects. We also found that a booster injection is efficacious in reactivating immunological memory to spike protein in naïve subjects, while it results ineffective in previously SARS-CoV-2 infected individuals. Finally, we observed a similar kinetics of decay of humoral and cellular immunity to SARS-CoV-2 up to one year following natural infection in a cohort of unvaccinated individuals. Conclusion: Short-term persistence of humoral immunity, together with the reduced neutralization capacity versus the currently prevailing SARS-CoV-2 variants, may account for reinfections and breakthrough infections. Long-lived memory B and CD4+ T cells may protect from severe disease development. A booster dose restores optimal anti-spike immunity in naïve subjects, while the need for vaccinated COVID-19 recovered subjects has yet to be defined. Trial registration: naFUNDING. This study was supported by funds to the Department of Experimental and Clinical Medicine, University of Florence (Project Excellence Departments 2018-2022), by the University of Florence, project RICTD2122, by the Italian Ministry of Health (COVID-2020-12371849) and by Tuscany Region (TagSARS CoV 2).