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

Context: Estimating the magnitude of the genetic contribution to the overal l variation of antibody levels among individuals should help clarify the ro le of genetic association in the biological mechanism of vaccine response a nd failure. This, in turn, should help guide the design of improved vaccine s 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 m onozygotic. Interventions: Determinations of zygosity, vaccine status, and quantitative IgG to measles, mumps, and rubella. Main outcome measure: Heritability (ratio of genetic variance to total vari ance). Results: The number of vaccine-doses, the age at initial immunization, and the time between immunization and sampling did not differ between monozygot ic and dizygotic twin pairs. The genetic variance - the variance in antibod y levels presumably due to genetic effects was 0.49 for measles, 0.54 for m umps, 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% wit h a lower bound of 4.94%,. Conclusion: Our data support the concept that genetic influences play a sub stantial role in the variation of antibody levels following immunization ag ainst measles and, to a lesser extent, mumps and rubella. (C) 2001 Elsevier Science Ltd. All rights reserved.