The role of HLA–DR–DQ haplotypes in variable antibody responses to Anthrax Vaccine Adsorbed
| Autor: | Inna G. Ovsyannikova, Wei Song, Vernon S. Pankratz, Jianming Tang, Robert M. Jacobson, Scott D. Parker, G.A. Poland, Richard A. Kaslow, Robert P. Kimberly, Kui Zhang, Brett A. McKinney, Jeffrey C. Edberg, Nicholas M. Pajewski |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Genotype Immunology Anthrax Vaccines Human leukocyte antigen Biology Polymorphism Single Nucleotide Article Anthrax Gene Frequency HLA-DQ Antigens Genetic variation Genetics Humans Alleles Genetics (clinical) Aged Anthrax vaccines HLA-DQ Antigen Histocompatibility Antigens Class I Haplotype Genetic Variation Anthrax Vaccine Adsorbed HLA-DR Antigens Middle Aged Virology Vaccination Bacterial vaccine Haplotypes Immunoglobulin G Antibody Formation Female |
| Zdroj: | Genes & Immunity. 12:457-465 |
| ISSN: | 1476-5470 1466-4879 0011-9067 |
| DOI: | 10.1038/gene.2011.15 |
| Popis: | Host genetic variation, particularly within the human leukocyte antigen (HLA) loci, reportedly mediates heterogeneity in immune response to certain vaccines; however, no large study of genetic determinants of anthrax vaccine response has been described. We searched for associations between the immunoglobulin G antibody to protective antigen (AbPA) response to Anthrax Vaccine Adsorbed (AVA) in humans, and polymorphisms at HLA class I (HLA-A, -B, and -C) and class II (HLA-DRB1, -DQA1, -DQB1, -DPB1) loci. The study included 794 European-Americans and 200 African-Americans participating in a 43-month, double-blind and placebo-controlled clinical trial of AVA (clinicaltrials.gov identifier NCT00119067). Among European-Americans, genes from tightly linked HLA-DRB1, -DQA1, -DQB1 haplotypes displayed significant overall associations with longitudinal variation in AbPA levels at 4, 8, 26 and 30 weeks from baseline in response to vaccination with three or four doses of AVA (global P=6.53 × 10(-4)). In particular, carriage of the DRB1-DQA1-DQB1 haplotypes (*)1501-(*)0102-(*)0602 (P=1.17 × 10(-5)), (*)0101-(*)0101-(*)0501 (P=0.009) and (*)0102-(*)0101-(*)0501 (P=0.006) was associated with significantly lower AbPA levels. In carriers of two copies of these haplotypes, lower AbPA levels persisted following subsequent vaccinations. No significant associations were observed amongst African-Americans or for any HLA class I allele/haplotype. Further studies will be required to replicate these findings and to explore the role of host genetic variation outside of the HLA region. |
| Databáze: | OpenAIRE |
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