Systems Vaccinology: Enabling Rational Vaccine Design with Systems Biology

Despite their great success, we understand little about how effective vaccines stimulate protective immune responses. Two recent developments promise to yield such understanding: the appreciation of the crucial role of the innate immune system in sensing microorganisms and tuning immune responses, and advances in systems biology. In this presentation, I will discuss how these developments are yielding insights into the mechanism of some of the most successful vaccines ever developed. Furthermore, such developments promise to address a major challenge in vaccinology: that the efficacy of a vaccine can only be ascertained retrospectively, upon infection. The identification of molecular signatures induced rapidly after vaccination, which correlate with and predict the later development of protective immune responses, would represent a strategy to prospectively determine vaccine efficacy. Such a strategy would be particularly useful when evaluating the efficacy or immunogenicity of untested vaccines, or in identifying individuals with sub-optimal responses amongst high risk populations, such as infants or the elderly. We have recently used a systems biology approach to identify early gene signatures that correlate with, and predict the later immune responses in humans vaccinated with the live attenuated yellow fever vaccine YF-17D, or with the influenza vaccines. I will review these studies, and discuss their broader implications for vaccinology.