The relationship between immunogenicity and reactogenicity of vaccines

This narrative review by Gromer et al. provides a comprehensive synthesis of the long-observed but poorly characterized relationship between vaccine reactogenicity—short-term, inflammatory adverse events—and immunogenicity, the adaptive immune response generated after vaccination. Spanning studies of traditional live-attenuated vaccines to contemporary mRNA platforms, the review argues that although evidence is heterogeneous, a modest positive association between systemic reactogenicity and humoral immunogenicity is consistently detectable across several pathogens and vaccine types. The authors weave historical data, mechanistic insights, and methodological considerations to highlight the evolving understanding of this relationship and its implications for vaccine development, public communication, and precision vaccinology. The review first surveys early evidence from live-attenuated vaccines such as smallpox, BCG, measles, and rubella. These foundational studies frequently revealed correlations between visible local or systemic reactions and heightened antibody responses. For example, early smallpox vaccination experiments in animals showed that the presence of a characteristic vesicular lesion predicted protective immunity, clearly...