The genetic basis for interindividual immune response variation to measles vaccine: new understanding and new vaccine approaches

Abstract

The live-attenuated measles vaccine is effective, but measles outbreaks still occur in vaccinated populations. This warrants elucidation of the determinants of measles vaccine-induced protective immunity. Interindividual variability in markers of measles vaccine-induced immunity, including neutralizing antibody levels, is regulated in part by host genetic factor variations. This review summarizes recent advances in our understanding of measles vaccine immunogenetics relative to the perspective of developing better measles vaccines. Important genetic regulators of measles vaccine-induced immunity, such as HLA class I and HLA class II genotypes, single nucleotide polymorphisms in cytokine/cytokine receptor genes (IL12B, IL12RB1, IL2, IL10) and the cell surface measles virus receptor CD46 gene, have been identified and independently replicated. New technologies present many opportunities for identification of novel genetic signatures and genetic architectures. These findings help explain a variety of immune response-related phenotypes and promote a new paradigm of ‘vaccinomics’ for novel vaccine development.

Immune activation alters cellular and humoral responses to yellow fever 17D vaccine

“…We found in this study that neither gender nor viremia affected the YF-17D response. We cannot rule out the impact of polymorphisms in genes involved in cytokines or HLA molecules in the vaccine response (36)(37)(38)(39). Studies with greater numbers of volunteers would be required to address their effect on the YF-17D response.…”

Mortality among recipients of the Merck V710 Staphylococcus aureus vaccine after postoperative S. aureus infections: An analysis of possible contributing host factors

“…Immunization with IsdB in a predisposed host without circulating IL2 could lead to commission of an original antigenic sin fostering a misdirected and suboptimal Th2-biased immune response to subsequent natural infection. 11,[15][16][17][18] The coincidence of 3 factors (low prevaccination IL-2 levels, receipt of V710, and postoperative S. aureus infection) appeared to be necessary and sufficient to substantially increase the mortality rate in our study population after major cardiothoracic surgery. All 12 V710 recipients (but only 1/13 placebo recipients) in our sample with undetectable serum IL2 concentrations prior to vaccination who then developed a postoperative S. aureus infection died.…”

Searching for the human genetic factors standing in the way of universally effective vaccines

“…The majority of the studies that have been published looking at these vaccines have been undertaken by a single group and have been reviewed extensively elsewhere [78,79], but there has been a series of more recent studies looking at these vaccines which have resulted in some interesting new observations. A large discovery GWAS has been completed looking at RV demonstrating again that the HLA-DPB1 locus is likely to be associated with rubella neutralization antibody response [38].…”