Genetic regulation of immune responses to vaccines in early life

Abstract

Infant immunization is the most cost-effective strategy to prevent infectious diseases in childhood, but is limited by immaturity of the immune system. To define strategies to improve vaccine immunogenicity in early life, the role of genetic and environmental factors in the control of vaccine responses in infant twins was studied. Immune responses to BCG, polio, hepatitis B, diphtheria, pertussis and tetanus vaccines were measured at 5 months of age in 207 Gambian twin pairs recruited at birth. Intrapair correlations for monozygous and dizygous pairs were compared to estimate the environmental and genetic components of variation in responses. High heritability was observed for antibody (Ab) responses to hepatitis B (77%), oral polio (60%), tetanus (44%) and diphtheria (49%) vaccines. Significant heritability was also observed for interferon-g and interleukin-13 responses to tetanus, pertussis and some BCG vaccine antigens (39-65%). Non-HLA genes played a dominant role in responses to Ab-inducing vaccines, whereas responses to BCG were predominantly controlled by genes within the HLA class II locus. Genetic factors, particularly non-HLA genes, significantly modulate immune responses to infant vaccination. The identification of the specific genes involved will provide new targets for the development of vaccines and adjuvants for young infants that work independently of HLA.

New genetic associations detected in a host response study to hepatitis B vaccine

“…7,9 One non-MHC gene emerges with highly compelling evidence of support in our study, FOXP1. FOXP1 is a transcription factor that is instrumental in regulating development of the antibody producing B cell.…”

“…3 The reasons for these individual failures are multiple, including physical factors such as age, gender, obesity, immunosuppression and smoking 4,5 as well as variation in genes of the immune system. [6][7][8][9] Several polymorphisms of the human leukocyte antigen (HLA) loci have been linked to variations in the immune response both to vaccination as well as natural hepatitis B infections. In particular, HLA-DR3 and DR7, which are in linkage disequilibrium with HLA-DQ2, have been shown to be associated with nonresponsiveness, 10,11 whereas DRB1* alleles 1, 11 and 15 have been shown to be associated with a good response to HBV vaccination.…”

Factors influencing innate immunity and vaccine responses in infancy

“…It has to be assumed of course that some heterogeneity of observed vaccine responses can be ascribed to host genetic factors [38]. Marchant et al [39] measured antibody responses to tetanus toxoid, measles and total IgG in 210 Gambian twin pairs in The Gambia.…”

Human leukocyte antigen and interleukin 2, 10 and 12p40 cytokine responses to measles: Is there evidence of the HLA effect?

“…These negative cytokine secretion results may also be related to the HLA class I and class II alleles that vary in their capacity to stimulate cytokine production by CD8 and CD4 T cells, or that other non-HLA genes may play a role during measles virus antigen processing and presentation [42]. It is possible that cryopreserved PBMC did indeed secrete cytokines, but at levels that were below the sensitivity range of the immunoassay (minimum detection of 4 pg/ml).…”