Innate immune response after BNT162b2 COVID-19 vaccination associates with reactogenicity

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BackgroundThe innate immune response is important for the development of the specific adaptive immunity, however it may also be associated with reactogenicity after vaccination. We explore the association between innate responsiveness, reactogenicity, and antibody response after first COVID-19 vaccination. MethodsWe included 146 healthy Dutch individuals aged 12–59 who received their first BNT162b2 (Comirnaty, Pfizer) COVID-19 vaccination. Data on reactogenicity were collected for each individual through daily questionnaires from day 0–5 after vaccination. From 60 participants, serum (adults) and plasma (adolescents) samples were collected before and/or 2 ± 1 days after vaccination to measure cytokines/chemokines as markers for innate responsiveness. Each individual was categorised into innate low, intermediate and high responder based on above or below the median value for each analyte detected after vaccination. For 137 participants, serum was collected at day 28 after vaccination for Spike S1- and RBD-antibody concentration. The associations between reactogenicity and/or innate responsiveness and/or log-transformed antibody concentration were explored using logistic and linear regressions. ResultsMost participants (85 %) reported both local and systemic symptoms after vaccination. Two participants reported no symptoms. More than half (54 %) reported one or more moderate symptoms. Significantly higher levels of pro-inflammatory mediators CXCL9, CXCL10, CXCL11, IFNγ and CCL20 in adults, and CXCL9, CXCL10 and CXCL11 in adolescents, were found after vaccination. Participants who showed high innate immune responsiveness had higher odds (OR 6.0; 95 % CI 1.4–33) of experiencing one or more moderate symptoms. No association was found between innate responsiveness or having one or more moderate symptoms with Spike S1- or RBD-antibody concentration at day 28 after vaccination. ConclusionOur results suggest an association between the strength of the innate immune response and the severity of reactogenicity to SARS-CoV-2 vaccination. However, more research is needed to understand the relation between reactogenicity and immunogenicity of COVID-19 vaccines.