Longitudinal Evaluation of Severe Acute Respiratory Syndrome Coronavirus 2 T-Cell Immunity Over 2 Years Following Vaccination and Infection
Authors: Juhl Anna Karina , Dietz Lisa Loksø , Søgaard Ole Schmeltz , Reekie Joanne , Nielsen Henrik , Johansen Isik Somuncu , Benfield Thomas , Wiese Lothar , Stærke Nina Breinholt , Jensen Tomas Østergaard , Olesen Rikke , Iversen Kasper , Fogh Kamille , Bodilsen Jacob , Madsen Lone Wulff , Lindvig Susan Olaf , Raben Dorthe , Andersen Sidsel Dahl , Hvidt Astrid Korning , Andreasen Signe Rode , Baerends Eva Anna Marianne , Lundgren Jens , Østergaard Lars , Tolstrup Martin ,   for the ENFORCE Study Group, Lundgren J , Østergaard L J , Benfield T , Krohn-Dehli L , Petersen D K , Fogh K , Mikkelsen E H , Iversen K , Bek P , Klastrup V , Larsen F , Rasmussen S H , Schleimann M H , Schieber S , Stærke N B , Søndergaard A , Tarp B , Tousgaard M , Yehdego Y , Bodilsen J , Nielsen H , Petersen K T , Juhl M R , Thisted R K , Caspersen S F , Iversen M , Knudsen L S , Meyerhoff J L , Sander L G , Wiese L , Abildgaard C , Holden I K , Johansen N E , Johansen I S , Larsen L , Lindvig S O , Madsen L W , Øvrehus A , Kruse N A , Lomholdt H , Krause T G , Valentiner-Branth P , Søborg B , Fischer T K , Erikstrup C , Ostrowski S R , Nielsen H , Johansen I S , Østergaard L J , Tolstrup M , Stærke N B , Søgaard O S , Wiese L , Benfield T , Lundgren J , Raben D , Nielsen H , Johansen I S , Østergaard L J , Tolstrup M , Stærke N B , Søgaard O S , Wiese L , Benfield T , Lundgren J , Raben D , Jylling E , Hougaard D , Andersen S D , Lykkegaard K , Stærke N B , Søgaard O S , Tolstrup M , Østergaard L J , Andreasen S R , Baerends E , Dietz L L , Hvidt A K , Juhl A K , Olesen R , Tolstrup M , Andersen K K , Bannister W , Bjernved C , Elsing T W , Esmann F V , Ghafari M A , Gravholdt E , Jakobsen S F , Jakobsen M L , Jensen C M , Jensen T Ø , Kristensen D , Kumar L R , Lundgren J , Matthews C , Normand N , Olsson C , Raben D , Reekie J , Traytel A , Weide T , Hvas A M , Støvring H , Erikstrup C , Krause T G , Fischer T K , Ostrowsky S 
Published: April 2024

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.