The role of systems biology approaches in determining molecular signatures for the development of more effective vaccines

ABSTRACT

Introduction: Emerging infectious diseases are a major threat to public health, and while vaccines have proven to be one of the most effective preventive measures for infectious diseases, we still do not have safe and effective vaccines against many human pathogens, and emerging diseases continually pose new threats. The purpose of this review is to discuss how the creation of vaccines for these new threats has been hindered by limitations in the current approach to vaccine development. Recent advances in high-throughput technologies have enabled scientists to apply systems biology approaches to collect and integrate increasingly large datasets that capture comprehensive biological changes induced by vaccines, and then decipher the complex immune response to those vaccines.

Areas covered: This review covers advances in these technologies and recent publications that describe systems biology approaches to understanding vaccine immune responses and to understanding the rational design of new vaccine candidates.

Expert opinion: Systems biology approaches to vaccine development provide novel information regarding both the immune response and the underlying mechanisms and can inform vaccine development.

KEYWORDS:

• Systems biology
• vaccines
• viral vaccines
• vaccination
• vaccine development
• immunology
• gene expression profiling
• genomics
• proteomics

Article highlights

• Systems biology is being applied to studies of vaccine-induced immune responses.

• Such studies have led to novel insights into how immunity is generated to viral vaccines.

• Newer assays are being incorporated into systems-level studies. This includes single-cell techniques, RNA- and DNA-based assays, epigenetics, and massive cytokine/chemokine and flow cytometry measures, as well as others.

• Bioinformatic approaches that are reproducible, standardized, and validated are needed to better interpret the results of systems-level studies.

• The end goal of systems vaccinology is deep insight into how vaccine-induced immunity is generated, and identification of barriers to developing such immunity; in turn, this will allow reverse-engineering of novel vaccine candidates.

Declaration of interest

G A Poland is the chair of a Safety Evaluation Committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. G A Poland offers consultative advice on vaccine development to Merck & Co. Inc., Avianax, Adjuvance, Valneva, Medicago, Sanofi Pasteur, GlaxoSmithKline, and Emergent Biosolutions. G A Poland and I G Ovsyannikova hold four patents related to vaccinia and measles peptide research. R B Kennedy has received funding from Merck Research Laboratories to study waning immunity to mumps vaccine. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policies. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award numbers R01AI127365, R01AI033144, R01 AI121054, R37AI048793, N01AI40065, and U01AI089859. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.