Local and systemic reactogenicity after mRNA and protein-based COVID-19 vaccines compared to meningococcal vaccine (MenACWY) in a UK blinded, randomized phase 2 trial (COV-BOOST).

Reactogenicity, the occurrence of vaccine side effects, can impact vaccine acceptance. There is limited data comparing the reactogenicity of COVID-19 vaccines to other routinely used vaccines, such as the meningococcal conjugate vaccine (MenACWY). In a trial of UK adults, participants received a third COVID-19 vaccine dose (NVX-CoV2373, BNT162b2, or mRNA1273) alongside MenACWY as an active control. Compared to MenACWY, we found that mRNA vaccines, particularly mRNA1273, showed the greatest relative increase in side effects, while protein-based NVX-CoV2373 generally elicited similar reactogenicity to MenACWY. These findings suggest that platform type can influence vaccine reactogenicity, and further research is needed to compare COVID-19 vaccines with other routinely administered vaccines.