Adversomics: a new paradigm for vaccine safety and design

Abstract

Despite the enormous population benefits of routine vaccination, vaccine adverse events (AEs) and reactions, whether real or perceived, have posed one of the greatest barriers to vaccine acceptance – and thus to infectious disease prevention – worldwide. A truly integrated clinical, translational, and basic science approach is required to understand the mechanisms behind vaccine AEs, predict them, and then apply this knowledge to new vaccine design approaches that decrease, or avoid, these events. The term ‘adversomics’ was first introduced in 2009 and refers to the study of vaccine adverse reactions using immunogenomics and systems biology approaches. In this review, we present the current state of adversomics research, review known associations and mechanisms of vaccine AEs/reactions, and outline a plan for the further development of this emerging research field.

Keywords:

• drug-related side effects and adverse reactions
• genetic association studies
• genomics
• immunogenetics
• individualized medicine
• polymorphism
• single nucleotide
• systems biology
• vaccination
• vaccines
• viral vaccines

Financial & competing interests disclosure

The authors were supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award numbers U01AI089859, N01AI40065, R37AI048793, and R01AI033144. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. GA Poland is the chair of a Safety Evaluation Committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. GA Poland offers consultative advice on vaccine development to Merck & Co. Inc., CSL Biotherapies, Avianax, Sanofi Pasteur, Dynavax, Novartis Vaccines and Therapeutics, PAXVAX Inc, Emergent Biosolutions, Adjuvance, and Vaxness. GA Poland and IG Ovsyannikova hold two patents related to vaccinia and measles peptide research. JA Whitaker receives funding for Mayo Clinic research from Pfizer Independent Grants for Learning and Change. 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 apart from those disclosed.

Key issues

• Adversomics is the application of immunogenomics and systems biology approaches to understand the genetic and non-genetic drivers of vaccine adverse reactions at the molecular level.

• Understanding and preventing serious adverse vaccine reactions is critical to improving public trust in vaccine safety and to developing new safe and effective vaccines.

• Vaccine immunogenicity and vaccine adverse events have been reported at higher rates for females than males for multiple vaccines. This observation warrants further evaluation.

• International partnerships between clinicians, public health officials, epidemiologists and clinical, translational and basic science researchers are needed to advance the field of adversomics.

• An international biobank of specimens from patients with vaccine adverse events needs to be created in order to conduct further adversomics studies.