Overcoming limitations in the systems vaccinology approach: a pathway for accelerated HIV vaccine development

There remains a pressing need for an efficacious vaccine to combat HIV. The burgeoning fields of systems biology and innate immunity, as harnessed in systems vaccinology, promise to accelerate the discovery process and meet this need.

The tools of systems biology are increasingly employed to define innate immune responses to vaccination and thereby unmask early signaling events that control induced adaptive immunity. These studies involve a wide array of measurements, including transcriptomics and proteomics, and a wide array of biological systems, from in-vitro stimulated murine innate immune cells to whole blood collected from vaccinated human donors. Each measurement and each system offers unique insights as well as special limitations and challenges.

A holistic consideration of the models available for intensive HIV systems vaccinology analysis identifies a suite of interlocking opportunities and constraints. Although the murine system enables detailed mechanistic analysis, vaccine efficacy cannot be assessed in this model. Systems analysis of blood donated by vaccinated humans permits identification of immunogenicity signatures and biomarkers, but deriving direct mechanisms from these indirect measurements is precarious. The goals of HIV systems vaccinology may be best met by judicious integration of in vitro, in vivo (murine and nonhuman primate), and human clinical analyses.