Systems vaccinology: its promise and challenge for HIV vaccine developmentNakaya, Helder I.a,b; Pulendran, Balia,b,cCurrent Opinion in HIV & AIDS: January 2012 - Volume 7 - Issue 1 - p 24–31 doi: 10.1097/COH.0b013e32834dc37b SYSTEMS BIOLOGY IN UNDERSTANDING HIV PATHOGENESIS AND GUIDING VACCINE DEVELOPMENT: Edited by Rafick-Pierre Sekaly and Bali Pulendran Abstract Author Information Purpose of review: The use of systems biology approaches to understand and predict vaccine-induced immunity promises to revolutionize vaccinology. For centuries vaccines were developed empirically, with very little understanding of the mechanisms by which they mediate protective immunity. The so-called systems vaccinology approach employs high-throughput technologies (e.g. microarrays, RNA-seq and mass spectrometry-based proteomics and metabolomics) and computational modeling to describe the complex interactions between all the parts of immune system, with a view to elucidating new biological rules capable of predicting the behavior of the system. Recent findings: Systems biology successfully applied to yellow-fever and influenza vaccines has led to the discovery of signatures that predict vaccine immunogenicity, and promises to advance basic immunology research by providing novel mechanistic insights about immune regulation. However a major challenge of systems vaccinology concerns the analyses and interpretation of the large and noisy data sets generated by high-throughput techniques. Overcoming these issues, we envision that systems vaccinology will have a potential impact on vaccine development, including HIV vaccines. Summary: High-throughput technologies allow the investigation of vaccine-induced immune responses at system and molecular levels. These are currently being used to unravel new molecular insights about the immune system, and are on the verge of being integrated into clinical trials to enable rational vaccine design and development. aEmory Vaccine Center bYerkes National Primate Research Center cDepartment of Pathology, Emory University School of Medicine, Georgia, USA Correspondence to Bali Pulendran, Emory Vaccine Center, 954 Gatewood Road, Atlanta, GA 30329, USA. Tel: +1 404 727 8945; e-mail: firstname.lastname@example.org © 2012 Lippincott Williams & Wilkins, Inc.