For more than a century, immunologists and vaccinologists have existed in parallel universes. Immunologists have for long reveled in using 'model
antigens', such as chicken egg
ovalbumin or nitrophenyl
haptens, to study immune responses in model organisms such as mice. Such studies have yielded many seminal insights about the mechanisms of immune regulation, but their relevance to humans has been questioned. In another universe, vaccinologists have relied on human clinical trials to assess
vaccine efficacy, but have done little to take advantage of such trials for studying the nature of immune responses to vaccination. The human model provides a
nexus between these two universes, and recent studies have begun to use this model to study the molecular profile of innate and adaptive responses to vaccination. Such 'systems vaccinology' studies are beginning to provide mechanistic insights about innate and adaptive immunity in humans. Here, we present an overview of such studies, with particular examples from studies with the
yellow fever and the seasonal
influenza vaccines. Vaccination with the
yellow fever vaccine causes a systemic acute
viral infection and thus provides an attractive model to study innate and adaptive responses to a primary viral challenge. Vaccination with the live attenuated
influenza vaccine causes a localized acute
viral infection in mucosal tissues and induces a recall response, since most vaccinees have had prior exposure to
influenza, and thus provides a unique opportunity to study innate and
antigen-specific memory responses in mucosal tissues and in the blood. Vaccination with the inactivated
influenza vaccine offers a model to study immune responses to an inactivated immunogen. Studies with these and other
vaccines are beginning to reunite the estranged fields of immunology and vaccinology, yielding unexpected insights about mechanisms of viral immunity.
Vaccines that have been proven to be of immense benefit in saving lives offer us a new fringe benefit: lessons in viral immunology.