Chapter 5 - Systems Vaccinology

Abstract

Effective vaccines for numerous pathogens—including malaria, tuberculosis (TB), and human immunodeficiency virus (HIV)—remain elusive despite decades of research. Scores of HIV vaccine strategies have been proposed, with more than 550 phase I trials registered at clinicaltrials.gov (April 24, 2016). However, just six phase IIb/III vaccine efficacy trials have been conducted, testing only four concepts. The main challenge for pathogens like HIV or TB is the lack of a straightforward pathway for advanced development because of the absence of a robust correlate of protection. Such a correlate of immunity that associates with the incidence of infection is crucial to guide the development of vaccines, as it provides a way to down-select vaccine candidates that fail to induce the desired immune response. As such, correlates of protection serve as the fundamental “go/no-go” criterion to advance candidates through early stages of development. Current strategies to better define vaccine correlates of immunity are moving beyond the standard characterization of cellular and humoral responses to also analyze host and microbial genetic parameters using systematic OMICS-guided approaches. These novel strategies harness the power of “big data” for the purpose of identifying vaccine candidates that offer the best chance of providing protective immunity.