(345) Mapping Genetic and Molecular Contributions to Vaccine Adverse Reactions: a systematic review of observational studies

Background: Vaccination undeniably plays an essential part in the world's health and has significantly reduced the incidence of infectious diseases. While most vaccine administrations produce protective immunity with no adverse events (AEs), some may have adverse events that vary in intensity and severity.

Objectives: This systematic review aims to synthesize existing studies investigating the genetic and molecular contributions (i.e., Omics approach) to vaccine-induced adverse events to enhance understanding of the diverse molecular pathways involved.

Methods: We incorporated articles from EMBASE, Pubmed, Cochrane, and Web of Science from inception until January 2023. The inclusion criteria encompassed studies exploring genetic and molecular factors contributing to vaccine-induced AEs through Omics approaches. Exclusions comprised case reports, reviews, and preclinical and in silico studies. Two independent researchers conducted data extraction and methodological quality assessment.

Results: Our search retrieved 3,961 deduplicated papers. From these, 51 involving 396,103 vaccinated were selected. Most studies were conducted in the United States or Finland (n=14 each) and included predominantly European (n=19) and Asian (n=15) ethnicities. Eleven studies did not specify any ethnicity. Among the selected studies, 54.6% (n=28) were case-control studies. Over 23 vaccines were examined, with antituberculosis (n=21), influenza (n=11), and COVID-19 (n=5) being the most frequently studied. The analysis identified up to 99 AEs and 154 Omic factors. Common AEs included fever (n=13), osteitis (n=8), local cutaneous symptoms (n=7), and lymphadenopathies (n=7). Genomic factors (108/154, 70.1%), such as genetic variations in the human leukocyte antigen (HLA) system and polymorphisms of interleukin (IL)- or Toll-like receptor (TLR)-encoding genes, predominated.

Conclusions: We analysed 51 studies with 396,103 patients and found diverse adverse events and Omic factors associated with vaccine-induced AEs. Our findings highlight the importance of future research to refine immunization strategies, focusing on molecular pathways and genomic factors, including HLA system variations and gene polymorphisms.