Genetics Linked to Immunity to Childhood Vaccines

A genome-wide study, conducted by researchers at the University of Oxford in the United Kingdom (U.K.), has linked a number of genetic variations with the level of protective antibodies generated following routine childhood immunizations. According to the researchers, further research may make it feasible to incorporate genetic tests into neonatal screening programs that can predict immunity to vaccines and, therefore, guide personalized vaccination regimens.

The two-stage genome-wide association study involving 3,602 children in the U.K. and the Netherlands investigated the link between genetic variation and levels of immunity to three routine childhood vaccinations: capsular group C meningococcal (MenC), Haemophilus influenzae type b (Hib) and tetanus toxoid (TT) vaccines. Results identified two genetic loci associated with the persistence of vaccine-induced immunity in immunized children. MenC immunity persistence was linked with single nucleotide polymorphisms (SNPs) in a region of the genome containing a family of signal-regulatory protein genes (SIRPA, SIRPB and SIRPG), which are involved in immunological signaling. TT-specific immunity persistence was linked with SNPs in the human leukocyte antigen (HLA)locus, which contains the genes coding for HLA molecules that present peptides to T cells, which in turn induce B cells to produce antibodies. “We also identified a region within the HLA gene complex that contained SNPs associated with the persistence of TT-specific IgG,” the researchers wrote. “Given their role, HLA genes have frequently been candidates in studies exploring the genetic determinants of vaccine responses.”

According to the researchers, the identified variants will likely account for just a fraction of all the genetic determinants that impact on vaccine-induced immunity persistence. “In our study, we estimated the heritability of vaccine-induced immunity to vary from 14 percent to 81 percent,” they noted. “TT immunity was estimated to be the most heritable of these measures … it is likely that the study of larger vaccine cohorts will yield more loci associated with immunity to vaccine antigens.”

In addition, the researchers pointed out their study included primarily Caucasian children, so it is not clear whether the results would apply to different ethnicities. “We are now carrying out in-depth investigations into the biology of the genetic variants we described in this study,” said Daniel O’Connor, PhD, a postdoctoral researcher at the department of pediatrics, University of Oxford, who is first author of the research team’s published paper. “We also planned further research, in larger cohorts of children and other populations that benefit from vaccination, to further our understanding of how our genetic makeup shapes vaccine responses.”