Twin studies of immunogenicity - Determining the genetic contribution to vaccine failure

Context: Estimating the magnitude of the genetic contribution to the overall variation of antibody levels among individuals should help clarify the role of genetic association in the biological mechanism of vaccine response and failure. This, in turn, should help guide the design of improved vaccines with enhanced efficacy. Objective: To explore the magnitude of genetic influence on antibody levels following measles, mumps and rubella vaccines. Design: Cross-sectional survey study. Setting: Olmsted County, Minnesota. Participants: Healthy twin-pairs. Of the 100 twin-pairs enrolled, 45 were monozygotic. Interventions: Determinations of zygosity, vaccine status, and quantitative IgG to measles, mumps, and rubella. Main outcome measure: Heritability (ratio of genetic variance to total variance). Results: The number of vaccine-doses, the age at initial immunization, and the time between immunization and sampling did not differ between monozygotic and dizygotic twin pairs. The genetic variance - the variance in antibody levels presumably due to genetic effects - was 0.49 for measles, 0.54 for mumps, and 0.13 for rubella. Heritability, the ratio of genetic variance to total variance, was 88.5% for measles, with the lower bound of a one-sided 95% confidence interval equal to 52.4%. The heritability was, for mumps, 38.8% with a lower bound of 1.60%. The heritability for rubella was 45.7% with a lower bound of 4.94%. Conclusion: Our data support the concept that genetic influences play a substantial role in the variation of antibody levels following immunization against measles and, to a lesser extent, mumps and rubella.