The last decade has witnessed tremendous progress in immunology and vaccinology, owing to several scientific and technological breakthroughs. Systems vaccinology is a field that has emerged at the forefront of vaccine research and development and provides a unique way to probe immune responses to vaccination in humans. The goals of systems vaccinology are to use systems-based approaches to define signatures that can be used to predict vaccine immunogenicity and efficacy and to delineate the molecular mechanisms driving protective immunity. The application of systems biological approaches in influenza vaccination studies has enabled the discovery of early signatures that predict immunogenicity to vaccination and yielded novel mechanistic insights about vaccine-induced immunity. Here we review the contributions of systems vaccinology to influenza vaccine development and critically examine the potential of systems vaccinology toward enabling the development of a universal influenza vaccine that provides robust and durable immunity against diverse influenza viruses.
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