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Observational Study
. 2021 Dec 17;39(51):7367-7374.
doi: 10.1016/j.vaccine.2021.10.074. Epub 2021 Nov 11.

BNT162b2 mRNA COVID-19 vaccine Reactogenicity: The key role of immunity

Pilar Vizcarra  1 , Johannes Haemmerle  2 , Hector Velasco  3 , Tamara Velasco  4 , Marina Fernández-Escribano  2 , Alejandro Vallejo  3 , José L Casado  5
Affiliations
Observational Study

BNT162b2 mRNA COVID-19 vaccine Reactogenicity: The key role of immunity

Pilar Vizcarra et al. Vaccine. .

Abstract

We examined the impact of pre-existing SARS-CoV-2-specific cellular immunity on BNT162b2 mRNA COVID-19 vaccine reactogenicity. Of 96 healthcare workers (HCWs), 76% reported any vaccine reaction (first dose: 70%, second dose: 67%), none of which was severe. Following first dose, systemic reactions were significantly more frequent among HCWs with past infection than in infection-naïve individuals, and among HCWs with pre-existing cellular immunity than in those without it. The rate of systemic reactions after second dose was 1.7 and 2.0-times higher than after first dose among infection-naïve HCWs and those without pre-existing cellular immunity, respectively. Levels of SARS-CoV-2-specific T-cells before vaccination were higher in HCWs with systemic reactions after the first dose than in those without them. BNT162b2 vaccine reactogenicity after first dose is attributable to pre-existing cellular immunity elicited by prior COVID-19 or cross-reactivity. Reactogenicity following second dose suggests an immunity-boosting effect. Overall, these data may reduce negative attitudes towards COVID-19 vaccines. Study Registration. The study was registered on clinicaltrials.gov, NCT04402827.

Keywords: BNT162b2 mRNA vaccine; Booster effect; COVID-19; Reactogenicity; SARS-CoV-2; T-cell responses.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Quantitative analysis of SARS-CoV-2-specific T-cell immunity in healthcare workers before vaccination according to past infection. Percentage of interferon gamma-producing (INFγ + ) CD8 + and CD4 + T-cells induced by peptides spanning the immunogenic domains of the SARS-CoV-2 spike, membrane, and nucleocapsid proteins in peripheral blood mononuclear cells of healthcare workers before vaccination. Data are stratified by history of SARS-CoV-2 infection among all participants (A), and by disease severity among participants with past infection (B). Asympt. = asymptomatic SARS-CoV-2 infection. The horizontal lines represent medians with interquartile ranges. Comparisons between groups were performed using the Mann-Whitney U test.
Fig. 2
Fig. 2
Reactogenicity of BNT162b2 mRNA COVID-19 vaccine among healthcare workers. Comparison of vaccine-induced local and systemic reactions after the first dose (A, C, and E) and second dose (B, D, and F) of BNT162b2 mRNA vaccine. Data are presented as percentages and stratified by history of SARS-CoV-2 infection (A and B), COVID-19 severity (C and D), and pre-existing cellular immunity (E and F). Comparisons between groups were performed using the Mann-Whitney U test.
Fig. 3
Fig. 3
Quantitative analysis of SARS-CoV-2-specific pre-existing T-cell immunity in healthcare workers with and without BNT162b2 mRNA COVID-19 vaccine reactogenicity. Percentage of interferon gamma-producing (INFγ + ) CD8 + and CD4 + T-cells induced by peptides spanning the immunogenic domains of the SARS-CoV-2 spike, membrane, and nucleocapsid proteins in peripheral blood mononuclear cells of healthcare workers before vaccination. Data are presented as self-reported local (A and C) and systemic reactions (B and D) after the first (A and B) and second (C and D) vaccine doses. Comparisons between groups were performed using the Mann-Whitney U test.
Fig. 4
Fig. 4
Risk of presenting systemic reactions after the BNT162b2 mRNA COVID-19 vaccine among healthcare workers by subgroups. Relative risk and 95% Confidence Interval for comparisons based on history of SARS-CoV-2 infection, COVID-19 severity, and pre-existing cellular immunity for the first (A) and second (B) vaccine dose.
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