Application Of Pharmacogenomics To Vaccines

Abstract

The field of pharmacogenomics and pharmacogenetics provides a promising science base for vaccine research and development. A broad range of phenotype/genotype data combined with highthroughput genetic sequencing and bioinformatics are increasingly being integrated into this emerging field of vaccinomics. This paper discusses the hypothesis of the 'immune response gene network' and genetic (and bioinformatic) strategies to study associations between immune response gene polymorphisms and variations in humoral and cellular immune responses to prophylactic viral vaccines, such as measles-mumps-rubella, influenza, HIV, hepatitis B and smallpox. Immunogenetic studies reveal promising new vaccine targets by providing a better understanding of the mechanisms by which gene polymorphisms may influence innate and adaptive immune responses to vaccines, including vaccine failure and vaccine-associated adverse events. Additional benefits from vaccinomic studies include the development of personalized vaccines, the development of novel vaccines and the development of novel vaccine adjuvants.

Vaccinomics: Current Findings, Challenges and Novel Approaches for Vaccine Development

“…We have in part previously discussed some of these examples in other publications (1)(2)(3)9). Several alleles of the HLA loci have been linked with "responder" and "non-responder" phenotypes after MMR vaccination.…”

“…Jin and Wang (26) state, "the lesson learned from HLA is that polymorphism can occur preferentially in the functional domains of a given molecule with dramatic effects on epitope selection and presentation." As previously mentioned, we synthesized these insights into the concept of the "immune response network theory" (9,22) stating that immunity to a vaccine is driven by the complex interactions of individual and groups of genes and epigenetic interactions, and therefore can be determined and, in the future, predicted (3,55).…”

“…By understanding these critical genetic determinants of immune response, we may develop the basis for an individualized approach to vaccination. In turn, understanding these genetic drivers could be used to enhance immune response, for example, in vaccine non-responders, and to inform new vaccine development (3,8,9).…”

“…Such studies are important in providing the data necessary to support and pursue the novel and translational approach of directed vaccinology (1)(2)(3)9). Epidemiological and family vaccine studies have shown familial aggregation.…”

“…Epidemiological and family vaccine studies have shown familial aggregation. Subsequently, many association studies have identified both HLA and non-HLA candidate gene markers, including genes in close linkage disequilibrium (LD) with the putative causative marker (3,9). These HLA and single-nucleotide polymorphism (SNP) findings emphasize the importance of identifying and replicating initial findings of genetic associations with vaccineinduced immune responses, as well as understanding the functional consequences of each gene/SNP association.…”