title: Searching for the human genetic factors standing in the way of universally effective vaccines.
abstract: Vaccines have revolutionized modern public health. The effectiveness of some vaccines is limited by the variation in response observed between individuals and across populations. There is compelling evidence that a significant proportion of this variability can be attributed to human genetic variation, especially for those vaccines administered in early life. Identifying and understanding the determinants of this variation could have a far-reaching influence upon future methods of vaccine design and deployment. In this review, we summarize the genetic studies that have been undertaken attempting to identify the genetic determinants of response heterogeneity for the vaccines against hepatitis B, measles and rubella. We offer a critical appraisal of these studies and make a series of suggestions about how modern genetic techniques, including genome-wide association studies, could be used to characterize the genetic architecture of vaccine response heterogeneity. We conclude by suggesting how the findings from such studies could be translated to improve vaccine effectiveness and target vaccination in a more cost-effective manner.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK alexander.mentzer@ndm.ox.ac.uk.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Mentzer
authors.affiliation: Department of Paediatrics, University of Oxford, Oxford OX3 9DU, UK Oxford Biomedical Research Centre, Oxford OX3 7LE, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: O'Connor
authors.affiliation: Department of Paediatrics, University of Oxford, Oxford OX3 9DU, UK Oxford Biomedical Research Centre, Oxford OX3 7LE, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pollard
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK Department of Paediatrics, University of Oxford, Oxford OX3 9DU, UK Oxford Biomedical Research Centre, Oxford OX3 7LE, UK.
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000917:Antibody Formation / Q000235:genetics; D003141:Communicable Diseases / Q000276:immunology*; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D014612:Vaccines / Q000276:immunology*
chemical_list: D014612:Vaccines
keywords: GWAS; gene; hepatitis B; measles; rubella; vaccine