The role of HLA-DR-DQ haplotypes in variable antibody responses to Anthrax Vaccine Adsorbed

N. M. Pajewski, S. D. Parker, G. A. Poland, I. G. Ovsyannikova, W. Song, K. Zhang, B. A. McKinney, V. S. Pankratz, J. C. Edberg, R. P. Kimberly, R. M. Jacobson, J. Tang, R. A. Kaslow

Research output: Contribution to journalArticle

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Abstract

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 P6.53 × 10 4). In particular, carriage of the DRB1-DQA1-DQB1 haplotypes 1501-0102-0602 (P1.17 × 10 5), 0101-0101-0501 (P<0.009) and 0102-0101-0501 (P0.006) 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.

Original languageEnglish (US)
Pages (from-to)457-465
Number of pages9
JournalGenes and Immunity
Volume12
Issue number6
DOIs
StatePublished - Sep 2011

Fingerprint

Anthrax Vaccines
HLA Antigens
Haplotypes
Antibody Formation
Antigens
Antibodies
African Americans
Vaccination
HLA-D Antigens
Controlled Clinical Trials
Vaccines
Immunoglobulin G
Alleles
Placebos

Keywords

  • anthrax vaccines
  • bacillus anthracis
  • bacterial vaccines
  • HLA antigens
  • vaccination

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

Pajewski, N. M., Parker, S. D., Poland, G. A., Ovsyannikova, I. G., Song, W., Zhang, K., ... Kaslow, R. A. (2011). The role of HLA-DR-DQ haplotypes in variable antibody responses to Anthrax Vaccine Adsorbed. Genes and Immunity, 12(6), 457-465. https://doi.org/10.1038/gene.2011.15

The role of HLA-DR-DQ haplotypes in variable antibody responses to Anthrax Vaccine Adsorbed. / Pajewski, N. M.; Parker, S. D.; Poland, G. A.; Ovsyannikova, I. G.; Song, W.; Zhang, K.; McKinney, B. A.; Pankratz, V. S.; Edberg, J. C.; Kimberly, R. P.; Jacobson, R. M.; Tang, J.; Kaslow, R. A.

In: Genes and Immunity, Vol. 12, No. 6, 09.2011, p. 457-465.

Research output: Contribution to journalArticle

Pajewski, NM, Parker, SD, Poland, GA, Ovsyannikova, IG, Song, W, Zhang, K, McKinney, BA, Pankratz, VS, Edberg, JC, Kimberly, RP, Jacobson, RM, Tang, J & Kaslow, RA 2011, 'The role of HLA-DR-DQ haplotypes in variable antibody responses to Anthrax Vaccine Adsorbed', Genes and Immunity, vol. 12, no. 6, pp. 457-465. https://doi.org/10.1038/gene.2011.15
Pajewski NM, Parker SD, Poland GA, Ovsyannikova IG, Song W, Zhang K et al. The role of HLA-DR-DQ haplotypes in variable antibody responses to Anthrax Vaccine Adsorbed. Genes and Immunity. 2011 Sep;12(6):457-465. https://doi.org/10.1038/gene.2011.15
Pajewski, N. M. ; Parker, S. D. ; Poland, G. A. ; Ovsyannikova, I. G. ; Song, W. ; Zhang, K. ; McKinney, B. A. ; Pankratz, V. S. ; Edberg, J. C. ; Kimberly, R. P. ; Jacobson, R. M. ; Tang, J. ; Kaslow, R. A. / The role of HLA-DR-DQ haplotypes in variable antibody responses to Anthrax Vaccine Adsorbed. In: Genes and Immunity. 2011 ; Vol. 12, No. 6. pp. 457-465.
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