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

doi:10.1038/gene.2011.15

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 journal › Article › peer-review

29 Scopus citations

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 language	English (US)
Pages (from-to)	457-465
Number of pages	9
Journal	Genes and Immunity
Volume	12
Issue number	6
DOIs	https://doi.org/10.1038/gene.2011.15
State	Published - Sep 2011

Keywords

HLA antigens
anthrax vaccines
bacillus anthracis
bacterial vaccines
vaccination

ASJC Scopus subject areas

Immunology
Genetics
Genetics(clinical)

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10.1038/gene.2011.15

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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. (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

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

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.",

keywords = "HLA antigens, anthrax vaccines, bacillus anthracis, bacterial vaccines, vaccination",

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

note = "Funding Information: Samples used in this study were made available through a clinical trial funded by the Centers for Disease Control and Prevention, including a supplemental grant to Dr Poland. This work was supported by the National Institute of Allergy and Infectious Diseases through contract N01-AI40068 (to Dr Kaslow). Dr Pajewski was supported by post-doctoral training Grant T32 HL072757 from the National Heart, Lung, and Blood Institute. The authors would like to thank Conrad Quinn, PhD, Charles Rose, PhD and Brian Plikaytis, MS for helpful conversations concerning the NCT00119067 trial data and Jelai Wang, MS and Vinodh Srinivasasainagendra, MS for informatics and data management assistance. They also gratefully acknowledge the other site principal investigators from the NCT00119067 trial for their efforts in data collection: Janiine Babcock, MD (Walter Reed Army Institute of Research), Wendy Keitel, MD (Baylor College of Medicine), and Harry Keyserling, MD (Emory University School of Medicine).",

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language = "English (US)",

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AU - Parker, S. D.

AU - Poland, G. A.

AU - Ovsyannikova, I. G.

AU - Song, W.

AU - Zhang, K.

AU - McKinney, B. A.

AU - Pankratz, V. S.

AU - Edberg, J. C.

AU - Kimberly, R. P.

AU - Jacobson, R. M.

AU - Tang, J.

AU - Kaslow, R. A.

N1 - Funding Information: Samples used in this study were made available through a clinical trial funded by the Centers for Disease Control and Prevention, including a supplemental grant to Dr Poland. This work was supported by the National Institute of Allergy and Infectious Diseases through contract N01-AI40068 (to Dr Kaslow). Dr Pajewski was supported by post-doctoral training Grant T32 HL072757 from the National Heart, Lung, and Blood Institute. The authors would like to thank Conrad Quinn, PhD, Charles Rose, PhD and Brian Plikaytis, MS for helpful conversations concerning the NCT00119067 trial data and Jelai Wang, MS and Vinodh Srinivasasainagendra, MS for informatics and data management assistance. They also gratefully acknowledge the other site principal investigators from the NCT00119067 trial for their efforts in data collection: Janiine Babcock, MD (Walter Reed Army Institute of Research), Wendy Keitel, MD (Baylor College of Medicine), and Harry Keyserling, MD (Emory University School of Medicine).

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N2 - 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.

AB - 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.

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KW - anthrax vaccines

KW - bacillus anthracis

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

Abstract

Keywords

ASJC Scopus subject areas

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