A large population-based association study between HLA and KIR genotypes and measles vaccine antibody responses.
Human antibody response to measles vaccine is highly variable in the population. Host genes contribute to inter-individual antibody response variation. The killer cell immunoglobulin-like receptors (KIR) are recognized to interact with HLA molecules and possibly influence humoral immune response to viral antigens. To expand on and improve our previous work with HLA genes, and to explore the genetic contribution of KIR genes to the inter-individual variability in measles vaccine-induced antibody responses, we performed a large population-based study in 2,506 healthy immunized subjects (ages 11 to 41 years) to identify HLA and KIR associations with measles vaccine-induced neutralizing antibodies. After correcting for the large number of statistical tests of allele effects on measles-specific neutralizing antibody titers, no statistically significant associations were found for either HLA or KIR loci. However, suggestive associations worthy of follow-up in other cohorts include B*57:01, DQB1*06:02, and DRB1*15:05 alleles. Specifically, the B*57:01 allele (1,040 mIU/mL; p = 0.0002) was suggestive of an association with lower measles antibody titer. In contrast, the DQB1*06:02 (1,349 mIU/mL; p = 0.0004) and DRB1*15:05 (2,547 mIU/mL; p = 0.0004) alleles were suggestive of an association with higher measles antibodies. Notably, the associations with KIR genotypes were strongly nonsignificant, suggesting that KIR loci in terms of copy number and haplotypes are not likely to play a major role in antibody response to measles vaccination. These findings refine our knowledge of the role of HLA and KIR alleles in measles vaccine-induced immunity.
Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, MN, United States of America.
Inna G
IG
Ovsyannikova
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, United States of America.
Daniel J
DJ
Schaid
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, United States of America.
Beth R
BR
Larrabee
Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, MN, United States of America.
Iana H
IH
Haralambieva
Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, MN, United States of America.
Richard B
RB
Kennedy
Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, MN, United States of America.
Gregory A
GA
Poland
D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology; D002648:Child; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006649:Histocompatibility Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D008457:Measles / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology* / Q000517:prevention & control; D008458:Measles Vaccine / Q000276:immunology*; D008459:Measles virus / Q000276:immunology*; D011159:Population Surveillance; D054340:Receptors, KIR / Q000235:genetics*; D055815:Young Adult
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D006649:Histocompatibility Antigens; D008458:Measles Vaccine; D054340:Receptors, KIR