Lipsky, James J.

Background Measles remains a public health threat in the United States with over 50,000 cases being reported from 1989 through 1991 with continued smaller outbreaks. Measles vaccine failure is in part to blame for these large-scale outbreaks. The human leukocyte antigen (HLA) genes are important determinants of immune response to measles virus and vaccine. To examine the influence that HLA polymorphisms may have on measles vaccine antibody response, we compared the distribution of HLA-DRB1 alleles between measles vaccine nonresponders and hyper-responders. Methods We determined the seroprevalence of measles antibody in 881 school children immunized with measles-mumps-rubella-II at age 15 months using a whole virus IgG EIA. We performed class II HLA-DR typing by PCR with sequence specific primers (PCR-SSP) on 81 nonresponders (IgG seronegative) and 65 hyper-responders (from the upper 10th percentile of IgG levels of all subjects). We then compared the distribution of alleles between nonresponders and hyper-responders. Results The distribution of HLA-DRB1 alleles among nonresponders compared to hyper-responders was significantly different ( p = 0.014). Nonresponders were significantly less likely to carry the HLA-DRB1*13 alleles than were hyper-responders (7.4% vs 16.2%; p = 0.02). Nonresponders also had an excess of HLA-DRB1*07 alleles (15.4% vs 6.2%; p = 0.015). Conclusions The absence of HLA-DRB1*13 alleles is associated with measles vaccine nonresponse. The absence of this allele has also been associated with susceptibility to other infectious diseases. The role of this gene in the immunogenetic response to infectious diseases requires further study.