Adenovirus-based but not mRNA-based vaccines transiently alter platelet count homeostasis in healthy subjects

ABSTRACT

Background: Nuclei acid-based COVID-19 vaccines have proved highly effective in reducing the risk of hospitalisation and death. As they were distributed for the first time on a large-scale population, the adenovirus-based vaccines were linked to a very rare thrombosis with thrombocytopenia syndrome and the interplay between vaccination and platelet activation gained increasing attention. Aim(s) To compare the effect of mRNA-based and adenovirus-based vaccines on platelets of young healthy adults. Method(s) We prospectively enrolled 15 healthy volunteers (53% females) who received two doses of the mRNA-based vaccine BNT162b2, 21 days apart, and 25 healthy volunteers (64% females) that received one dose of the adenovirus-based vaccine, AZD1222, followed by one dose of BNT162b2 and we studied their platelet response before and after each dose of the vaccine (3 and 10 days post-injection). Result(s) Subjects receiving the AZD1222 vaccine experienced a transient but significant 20% decrease of the platelet count 3 days after the first injection, which was not detected after the first dose of BNT162b2. The BNT162b2, but not the AZD1222, vaccine was followed by increased plasmatic thrombopoietin concentration and mean platelet volume, indicative of higher platelet turnover. Three days after the AZD1222 injection, basal platelet integrin activation was elevated, but P-selectin exposure was unchanged. Conversely, the BNT162b2 vaccine induced a gradual increase in platelet P-selectin exposure and platelet-leukocyte aggregate formation, which correlated with the ability of the vaccines to evoke neutralizing antibodies against the Sars-COV- 2 spike protein. Moreover, three days after the AZD1222 injection we detected a transient 10-fold increase of the plasmatic concentration of IFN-gamma, while BNT vaccination induced a progressive increase of IL-1beta. Conclusion(s) Based on these observations we propose that the adenovirus-based vaccines, not the mRNA-based vaccines, transiently impair platelet count homeostasis. Future studies will investigate how these distinct vaccine vectors and inflammatory profiles affect platelet consumption and platelet production.