The Top Five “Game Changers” in Vaccinology: Toward Rational and Directed Vaccine Development

Abstract

Despite the tremendous success of the classical ''isolate, inactivate, and inject'' approach to vaccine development, new breakthroughs in vaccine research are increasingly reliant on novel approaches that incorporate cutting edge technology and advances in innate and adaptive immunology, microbiology, virology, pathogen biology, genetics, bioinformatics, and many other disciplines in order to: (1) deepen our understanding of the key biological processes that lead to protective immunity, (2) observe vaccine responses on a global, systems level, and (3) directly apply the new knowledge gained to the development of next-generation vaccines with improved safety profiles, enhanced efficacy, and even targeted utility in select populations. Here we highlight five key components foundational to vaccinomics efforts: applied immunogenomics, next generation sequencing and other cutting-edge ''omics'' technologies, advanced bioinformatics and analysis techniques, and finally, systems biology applied to immune profiling and vaccine responses. We believe these ''game changers'' will play a critical role in moving us toward the rational and directed development of new vaccines in the 21st century.

Variability in Humoral Immunity to Measles Vaccine: New Developments

“…The “OMIC” technologies are capable of measuring gene expression, protein levels, epigenetic events, and metabolic processes at a comprehensive level [65]. Thus, it is now possible to simultaneously examine changes in essentially every gene, protein, or biological product in response to a given stimulus.…”

“…One can also consider (with regard to current knowledge) taking advantage of the RIG-I (DDX58) pathway and/or TLR agonists to boost innate immunity and elicit optimal protection (neutralizing antibody levels and cellular immunity) after measles immunization. The aforementioned immunogenetics, vaccinomics and systems vaccinology published reports [23, 65, 77–81], provide examples of how such studies might lead to new vaccine development (Box 2). …”

The composition of immune cells serves as a predictor of adaptive immunity in a cohort of 50‐ to 74‐year‐old adults

“…[58][59][60] Following from this concept, we believe that vaccinomics approaches integrating high dimensional data sets and predictive modelling will be crucial to understanding, at a systems level, how the immune system functions, as we have previously elucidated. [59][60][61][62] This understanding can then be applied towards the rational and directed development of better vaccines. …”

Enhancing vaccine safety capacity globally: A lifecycle perspective

“…In the context of vaccine safety, applying knowledge gained from basic science, clinical research and systems biology to direct patient care might eventually lead to routine screening tests or other procedures that guide healthcare providers' vaccination decisions in order to maximize benefit and minimize adverse reactions at the individual patient level. The logical extension is to harness systems biology and genetic research to guide vaccine development, possibly even the development of personalized vaccines for individual patients based on a unique genetic profile (91-93). Although these concepts might seem futuristic, it is interesting to note that advancing precision medicine was highlighted in President Barack Obama's 2015 State of the Union Address (94).…”