Distinct platelet crosstalk with adaptive and innate immune cells after adenoviral and mRNA vaccination against SARS-CoV-2

BACKGROUND: Genetic-based COVID-19 vaccines have proved to be highly effective in reducing the risk of hospitalization and death. Because they were first distributed in a large-scale population, the adenoviral-based vaccines were linked to a very rare thrombosis with thrombocytopenia syndrome, and the interplay between platelets and vaccinations increasingly gained attention. OBJECTIVES: The objective of this article was to study the crosstalk between platelets and the vaccine-induced immune response. METHODS: We prospectively enrolled young healthy volunteers who received the mRNA-based vaccine, BNT162b2 (n = 15), or the adenovirus-based vaccine, AZD1222 (n = 25) and studied their short-term platelet and immune response before and after vaccine injections. In a separate cohort, we retrospectively analyzed the effect of aspirin on the antibody response 1 and 5 months after BNT162b2 vaccination. RESULTS: Here, we show that a faster antibody response to either vaccine is associated with the formation of platelet aggregates with marginal zone-like B cells, a subset geared to bridge the temporal gap between innate and adaptive immunities. However, although the mRNA-based vaccine is associated with a more gradual and tolerogenic response that fosters the crosstalk between platelets and adaptive immunity, the adenovirus-based vaccine, the less immunogenic of the 2, evokes an antiviral-like response during which the platelets are cleared and less likely to cooperate with B cells. Moreover, subjects taking aspirin (n = 56) display lower antibody levels after BNT162b2 vaccination compared with matched individuals. CONCLUSION: Platelets are a component of the innate immune pathways that promote the B-cell response after vaccination. Future studies on the platelet-immune crosstalk post-immunization will improve the safety, efficacy, and strategic administration of next-generation vaccines.