Abstract

BACKGROUNDImmunization against SARS-CoV-2, the causative agent of COVID-19, occurs via natural infection or vaccination. However, it is currently unknown how long infection- or vaccination-induced immunological memory will last.METHODSWe performed a longitudinal evaluation of immunological memory to SARS-CoV-2 up to 1 year after infection and following mRNA vaccination in naive individuals and individuals recovered from COVID-19 infection.RESULTSWe found that memory cells are still detectable 8 months after vaccination, while antibody levels decline significantly, especially in naive individuals. We also found that a booster injection is efficacious in reactivating immunological memory to spike protein in naive individuals, whereas it was 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 1 year following natural infection in a cohort of unvaccinated individuals.CONCLUSIONShort-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. In naive individuals, a booster dose restored optimal anti-spike immunity, whereas the needs for vaccinated individuals who have recovered from COVID-19 have yet to be defined.FUNDINGThis study was supported by funds to the Department of Experimental and Clinical Medicine, University of Florence (Project Excellence Departments 2018–2022), the University of Florence (project RICTD2122), the Italian Ministry of Health (COVID-2020-12371849), and the region of Tuscany (TagSARS CoV 2).

Highlights

  • Immunization against SARS-CoV-2, the causative agent of coronavirus disease-19 (COVID-19) occurs via natural infection or vaccination

  • Neutralizing antibodies increased in naïve subjects up to month 1 after vaccination, while they reached the highest level in recovered COVID-19 individuals already after the first injection, remaining stable up to month 1 (Figure 1E left and middle panels)

  • We and others have previously shown that in recovered COVID-19 subjects one dose of mRNA vaccine is sufficient to achieve high levels of anti-spike immunity, higher than those observed in naïve subjects after two vaccine injections [3,8]

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Summary

Introduction

Immunization against SARS-CoV-2, the causative agent of coronavirus disease-19 (COVID-19) occurs via natural infection or vaccination. Real-world studies have shown that 6 months following the complete mRNA vaccination cycle, protection against COVID-19 is significantly reduced in all age groups, protection from severe disease and hospitalization remains high [6,7,8,9] This phenomenon may be the result of progressive waning of immune protection. We assessed the longevity of immunological memory to SARS-CoV-2 following natural infection up to one year in a cohort of unvaccinated individuals In this case, despite a decline in antibody levels, B and T cells memory responses were still detectable 12 months after infection.

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