SARS-CoV-2 infection and vaccination trigger long-lived B and CD4+ T lymphocytes with implications for booster strategies
Alessio Mazzoni, … , Gian Maria Rossolini, Francesco Annunziato
Alessio Mazzoni, … , Gian Maria Rossolini, Francesco Annunziato
Published February 9, 2022
Citation Information: J Clin Invest. 2022;132(6):e157990. https://doi.org/10.1172/JCI157990.
View: Text | PDF
Clinical Medicine COVID-19

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

Abstract

BACKGROUND Immunization 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.METHODS We 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.RESULTS We 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.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. 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.FUNDING This 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).

Authors

Alessio Mazzoni, Anna Vanni, Michele Spinicci, Giulia Lamacchia, Seble Tekle Kiros, Arianna Rocca, Manuela Capone, Nicoletta Di Lauria, Lorenzo Salvati, Alberto Carnasciali, Elisabetta Mantengoli, Parham Farahvachi, Lorenzo Zammarchi, Filippo Lagi, Maria Grazia Colao, Francesco Liotta, Lorenzo Cosmi, Laura Maggi, Alessandro Bartoloni, Gian Maria Rossolini, Francesco Annunziato

×

Figure 4

Longitudinal evaluation of spike-specific circulating T cells in naive individuals and individuals who have recovered from COVID-19.

Options: View larger image (or click on image) Download as PowerPoint
Longitudinal evaluation of spike-specific circulating T cells in naive i...
(A) Representative flow cytometric plots of spike-specific CD4+CD154+IFN-γ+ T cells in 1 naive individual (top) and 1 individual who has recovered from COVID-19 (bottom) before vaccination, before second injection, and after 1 and 8 months following the complete vaccination cycle. Longitudinal evaluation of frequencies of spike-specific T cells expressing CD154 and producing at least 1 cytokine (ck) among IL-2, IFN-γ, and TNF-α (B), CD154+IFN-γ+ (C), CD154+IL-2+ (D), and CD154+TNF-α+ (E) in naive individuals (red lines, left) and individuals who have recovered from COVID-19 (blue lines, middle). Cumulative data are represented (right) as mean ± SEM from 15 naive individuals and 15 individuals who have recovered from COVID-19. In B–E, data are shown after subtraction of the background, unstimulated condition. Red and blue asterisks (left and middle) refer to paired statistics within each study group compared with the previous time point in the kinetics calculated with Wilcoxon’s signed-rank test. Red and blue pound signs (left and middle) refer to paired statistics within each study group between baseline and 8 months, calculated with Wilcoxon’s signed-rank test. Black asterisks (right) represent unpaired statistics between naive individuals and individuals who have recovered from COVID-19 at each time point calculated with Mann-Whitney test. *P < 0.05; #P < 0.05; **P < 0.01; ##P < 0.01; ***P < 0.001.