Longitudinal Evaluation of Severe Acute Respiratory Syndrome Coronavirus 2 T-Cell Immunity Over 2 Years Following Vaccination and Infection
Anna Karina Juhl, Lisa Loksø Dietz, Ole S. Søgaard, Joanne Reekie, Henrik Nielsen, Işık Somuncu Johansen, Thomas Benfield, Lothar Wiese, Nina Breinholt Stærke, Tomas Ø. Jensen, Rikke Olesen, Kasper Iversen, Kamille Fogh, Jacob Bodilsen, Lone Wulff Madsen, Susan Olaf Lindvig, Dorthe Raben, Sidsel Dahl Andersen, Astrid Korning Hvidt, Signe Rode Andreasen, Eva Anna Marianne Baerends, Jens Lundgren, Lars Østergaard, Martin Tolstrup, for the ENFORCE Study Group, Jens Lundgren, Lars Østergaard, T Benfield, L. Krohn-Dehli, D. K. Petersen, Kamille Fogh, Emma H Mikkelsen, Kasper Iversen, Przemys aw Wyr bek, Vibeke Klastrup, F Larsen, S.H. Rasmussen, Mariane Høgsbjerg Schleimann, S. Schieber, N B Stærke, A. Søndergaard, Britta Tarp, M. Tousgaard, Yordanos Yehdego, Jacob Bodilsen, Henrik Nielsen, K.T. Petersen, Maria Ruwald Juhl, R. K. Thisted, S. F. Caspersen, Martin Iversen, Lene Surland Knudsen, James L. Meyerhoff, L. G. Sander, L Wiese, C F Abildgaard, Inge K. Holden, Nicholas Johansen, Işık Somuncu Johansen, Lise Langeland Larsen, Susan Olaf Lindvig, Lone Wulff Madsen, Anne Øvrehus, N Kruse, H. Lomholdt, Tyra Grove Krause, Palle Valentiner‐Branth, Bolette Søborg, Thea Kølsen Fischer, Christian Erikstrup, Sisse Rye Ostrowski, Henrik Nielsen, I S Johansen, L J Østergaard, M Tolstrup, Nina Breinholt Stærke, Ole S. Søgaard, Lothar Wiese, T Benfield, J Lundgren, D Raben, Henrik Nielsen, I S Johansen, L J Østergaard, M Tolstrup, Nina Breinholt Stærke, Ole S. Søgaard, L Wiese, T Benfield, J Lundgren, D Raben, E. Jylling, David M. Hougaard, Søren Due Andersen, K. Lykkegaard, Nina Breinholt Stærke, Ole S. Søgaard, M Tolstrup, L J Østergaard, Signe Rode Andreasen
Abstract
BACKGROUND: Within a year of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, vaccines inducing a robust humoral and cellular immune response were implemented worldwide. However, emergence of novel variants and waning vaccine-induced immunity led to implementation of additional vaccine boosters. METHODS: This prospective study evaluated the temporal profile of cellular and serological responses in a cohort of 639 SARS-CoV-2-vaccinated participants, of whom a large proportion experienced a SARS-CoV-2 infection. All participants were infection naïve at the time of their first vaccine dose. Proportions of SARS-CoV-2 spike-specific T cells were determined after each vaccine dose using the activation-induced marker assay, while levels of circulating SARS-CoV-2 antibodies were determined by the Meso Scale serology assay. RESULTS: We found a significant increase in SARS-CoV-2 spike-specific CD4+ and CD8+ T-cell responses following the third dose of a SARS-CoV-2 messenger RNA vaccine as well as enhanced CD8+ T-cell responses after the fourth dose. Furthermore, increased age was associated with a poorer response. Finally, we observed that SARS-CoV-2 infection boosts both the cellular and humoral immune response, relative to vaccine-induced immunity alone. CONCLUSIONS: Our findings highlight the boosting effect on T-cell immunity of repeated vaccine administration. The combination of multiple vaccine doses and SARS-CoV-2 infections maintains population T-cell immunity, although with reduced levels in the elderly.