System-wide approaches are now being applied to study vaccine responses, whose mechanisms of action, and failure, are not well understood. These works have repeatedly shown vaccine response to be an orchestrated process involving multiple arms of immunity most noticeable sensing and innate components. Prediction of vaccine responses based on system-wide measures is achievable, but challenges remain for robust population wide predictions based only on pre-vaccination measures, especially in partially efficacious vaccines such as influenza. This is especially true in older adults, who are often less responsive to vaccination and exhibit high level of variation compared to young in many components of immunity. Despite this increase in variation, most of the studies on aging use group averages of immune phenotypes to model immune system behavior. Using systems approaches, it is possible to exploit this variation to form distinguishable clusters of phenotypes within and across individuals to discover underlying immune states.
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