Learning to Appreciate Our Differences

(See the article by Reif et al., on pages 16–22.) Despite overall levels of genetic similarity and shared physiological characteristics across the species, humans vary quite a bit in their individual responses to biological stress and noxious stimuli. Sometimes variant responses are dramatic and clinically important. This is certainly the case with respect to the responses of humans to microbial pathogens and their antigens. The consequences of infection by a pathogen in a host population vary from benign to catastrophic, as a complex function of the host genetics, the history of prior exposures and experiences, the current state of immune activation (both local and systemic), and, probably, a variety of other factors, including host nutritional status and the composition and structure of the indigenous microbiota. Although typical responses to vaccines are favorable, occasional responses are pathologic and costly to the host. If these aberrant responses could be predicted and understood mechanistically (the first element does not necessarily require the second), we would be able to reduce the number and/or severity of vaccine adverse events (AEs), improve vaccine design, and create personalized strategies for eliciting immune protection. In this issue of the Journal, Reif et al. [1] address this goal and provide an opportunity to discuss challenges and possible solutions.