Human Leukocyte Antigens and Cellular Immune Responses to Anthrax Vaccine Adsorbed

Overview

Journal Infect Immun

Publisher American Society for Microbiology

Specialty Allergy & Immunology

Date 2013 May 8

PMID 23649091

Citations 13

Authors

Inna G Ovsyannikova

V Shane Pankratz

Robert A Vierkant

Nicholas M Pajewski

Conrad P Quinn

Richard A Kaslow

Robert M Jacobson

Gregory A Poland

Affiliations

Soon will be listed here.

Abstract

Interindividual variations in vaccine-induced immune responses are in part due to host genetic polymorphisms in the human leukocyte antigen (HLA) and other gene families. This study examined associations between HLA genotypes, haplotypes, and homozygosity and protective antigen (PA)-specific cellular immune responses in healthy subjects following immunization with Anthrax Vaccine Adsorbed (AVA). While limited associations were observed between individual HLA alleles or haplotypes and variable lymphocyte proliferative (LP) responses to AVA, analyses of homozygosity supported the hypothesis of a "heterozygote advantage." Individuals who were homozygous for any HLA locus demonstrated significantly lower PA-specific LP than subjects who were heterozygous at all eight loci (median stimulation indices [SI], 1.84 versus 2.95, P = 0.009). Similarly, we found that class I (HLA-A) and class II (HLA-DQA1 and HLA-DQB1) homozygosity was significantly associated with an overall decrease in LP compared with heterozygosity at those three loci. Specifically, individuals who were homozygous at these loci had significantly lower PA-specific LP than subjects heterozygous for HLA-A (median SI, 1.48 versus 2.13, P = 0.005), HLA-DQA1 (median SI, 1.75 versus 2.11, P = 0.007), and HLA-DQB1 (median SI, 1.48 versus 2.13, P = 0.002) loci, respectively. Finally, homozygosity at an increasing number (≥ 4) of HLA loci was significantly correlated with a reduction in LP response (P < 0.001) in a dose-dependent manner. Additional studies are needed to reproduce these findings and determine whether HLA-heterozygous individuals generate stronger cellular immune response to other virulence factors (Bacillus anthracis LF and EF) than HLA-homozygous subjects.

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References

Schaid D, Rowland C, Tines D, Jacobson R, Poland G . Score tests for association between traits and haplotypes when linkage phase is ambiguous. Am J Hum Genet. 2002; 70(2):425-34. PMC: 384917. DOI: 10.1086/338688. View

Quinn C, Sabourin C, Niemuth N, Li H, Semenova V, Rudge T . A three-dose intramuscular injection schedule of anthrax vaccine adsorbed generates sustained humoral and cellular immune responses to protective antigen and provides long-term protection against inhalation anthrax in rhesus macaques. Clin Vaccine Immunol. 2012; 19(11):1730-45. PMC: 3491539. DOI: 10.1128/CVI.00324-12. View

Wright J, Quinn C, Shadomy S, Messonnier N . Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009. MMWR Recomm Rep. 2010; 59(RR-6):1-30. View

Carrington M, Nelson G, Martin M, Kissner T, Vlahov D, Goedert J . HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage. Science. 1999; 283(5408):1748-52. DOI: 10.1126/science.283.5408.1748. View

Pajewski N, Parker S, Poland G, Ovsyannikova I, Song W, Zhang K . The role of HLA-DR-DQ haplotypes in variable antibody responses to anthrax vaccine adsorbed. Genes Immun. 2011; 12(6):457-65. PMC: 3165112. DOI: 10.1038/gene.2011.15. View

Wang C, Tang J, Song W, Lobashevsky E, Wilson C, Kaslow R . HLA and cytokine gene polymorphisms are independently associated with responses to hepatitis B vaccination. Hepatology. 2004; 39(4):978-88. DOI: 10.1002/hep.20142. View

Kennedy R, Ovsyannikova I, Vierkant R, Jacobson R, Poland G . Effect of human leukocyte antigen homozygosity on rubella vaccine-induced humoral and cell-mediated immune responses. Hum Immunol. 2009; 71(2):128-35. PMC: 2815167. DOI: 10.1016/j.humimm.2009.11.002. View

Ovsyannikova I, Ryan J, Vierkant R, OByrne M, Pankratz V, Jacobson R . Influence of host genetic variation on rubella-specific T cell cytokine responses following rubella vaccination. Vaccine. 2009; 27(25-26):3359-66. PMC: 2693348. DOI: 10.1016/j.vaccine.2009.01.079. View

Ovsyannikova I, Jacobson R, Vierkant R, Jacobsen S, Pankratz V, Poland G . The contribution of HLA class I antigens in immune status following two doses of rubella vaccination. Hum Immunol. 2004; 65(12):1506-15. DOI: 10.1016/j.humimm.2004.07.001. View

10.

Crowe S, Garman L, Engler R, Farris A, Ballard J, Harley J . Anthrax vaccination induced anti-lethal factor IgG: fine specificity and neutralizing capacity. Vaccine. 2011; 29(20):3670-8. PMC: 3233230. DOI: 10.1016/j.vaccine.2011.03.011. View

11.

Tang J, Costello C, Keet I, Rivers C, Leblanc S, Karita E . HLA class I homozygosity accelerates disease progression in human immunodeficiency virus type 1 infection. AIDS Res Hum Retroviruses. 1999; 15(4):317-24. DOI: 10.1089/088922299311277. View

12.

Pajewski N, Shrestha S, Quinn C, Parker S, Wiener H, Aissani B . A genome-wide association study of host genetic determinants of the antibody response to Anthrax Vaccine Adsorbed. Vaccine. 2012; 30(32):4778-84. PMC: 3387748. DOI: 10.1016/j.vaccine.2012.05.032. View

13.

Marano N, Plikaytis B, Martin S, Rose C, Semenova V, Martin S . Effects of a reduced dose schedule and intramuscular administration of anthrax vaccine adsorbed on immunogenicity and safety at 7 months: a randomized trial. JAMA. 2008; 300(13):1532-43. DOI: 10.1001/jama.300.13.1532. View

14.

Campbell J, Clement K, Wasserman S, Donegan S, Chrisley L, Kotloff K . Safety, reactogenicity and immunogenicity of a recombinant protective antigen anthrax vaccine given to healthy adults. Hum Vaccin. 2007; 3(5):205-11. DOI: 10.4161/hv.3.5.4459. View

15.

Little S, Ivins B, Webster W, Fellows P, Pitt M, Norris S . Duration of protection of rabbits after vaccination with Bacillus anthracis recombinant protective antigen vaccine. Vaccine. 2006; 24(14):2530-6. DOI: 10.1016/j.vaccine.2005.12.028. View

16.

Ovsyannikova I, Jacobson R, Vierkant R, OByrne M, Poland G . Replication of rubella vaccine population genetic studies: validation of HLA genotype and humoral response associations. Vaccine. 2009; 27(49):6926-31. PMC: 2783524. DOI: 10.1016/j.vaccine.2009.08.109. View

17.

Kwok W, Yang J, James E, Bui J, Huston L, Wiesen A . The anthrax vaccine adsorbed vaccine generates protective antigen (PA)-Specific CD4+ T cells with a phenotype distinct from that of naive PA T cells. Infect Immun. 2008; 76(10):4538-45. PMC: 2546819. DOI: 10.1128/IAI.00324-08. View

18.

Davila J, McNamara L, Yang Z . Comparison of the predicted population coverage of tuberculosis vaccine candidates Ag85B-ESAT-6, Ag85B-TB10.4, and Mtb72f via a bioinformatics approach. PLoS One. 2012; 7(7):e40882. PMC: 3398899. DOI: 10.1371/journal.pone.0040882. View

19.

Mustafa A, Lundin K, Oftung F . Human T cells recognize mycobacterial heat shock proteins in the context of multiple HLA-DR molecules: studies with healthy subjects vaccinated with Mycobacterium bovis BCG and Mycobacterium leprae. Infect Immun. 1993; 61(12):5294-301. PMC: 281314. DOI: 10.1128/iai.61.12.5294-5301.1993. View

20.

Pati N, Sukriti , Hissar S, Agrawal K, Rani R, Sarin S . Decrease in CD4+ T lymphocyte proliferation responses and enhanced CD150 cell expression in health care workers non-responsive to HBV vaccine. Vaccine. 2007; 25(10):1848-55. DOI: 10.1016/j.vaccine.2006.10.041. View