The anthrax vaccine: No new tricks for an old dog

Bienek, Diane R.; Loomis, Lawrence J; Biagini, Raymond E.

doi:10.4161/hv.5.3.7308

Cited by 14 publications

(8 citation statements)

References 40 publications

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“…Protective Antigen is a major component of the Anthrax Vaccine Adsorbed (AVA) (16,17). The vast majority of healthy subjects have had no exposure to this antigen.…”

Section: Introductionmentioning

confidence: 99%

Frequency of Epitope-Specific Naive CD4+ T Cells Correlates with Immunodominance in the Human Memory Repertoire

Kwok

Tan

Gillette

et al. 2012

The Journal of Immunology

107

120

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The frequency of epitope specific naïve CD4+ T cells in humans has not been extensively examined. In this study, a systematic approach was used to examine the frequency of CD4+ T cells that recognize the Protective Antigen of Bacillus anthracis in both Anthrax Vaccine Adsorbed vaccinees and non-vaccinees with HLA-DRB1*01:01 haplotypes. Three epitopes were identified that had distinct degrees of immunodominance in subjects that had received the vaccine. Average naïve precursor frequencies of T cells specific for these different epitopes in the human repertoire ranged from 0.2 to 10 per million naïve CD4+ T cells, which is comparable to precursor frequencies observed in the murine repertoire. Frequencies of protective Antigen-specific T cells were two orders of magnitude higher in immunized subjects than in nonvaccinees. The frequencies of epitope specific memory CD4+ T cells in vaccinees were directly correlated with the frequencies of precursors in the naïve repertoire. At the level of TCR usage, at least one preferred Vβ in the naïve repertoire was present in the memory repertoire. These findings implicate naïve frequencies as a crucial factor in shaping the epitope specificity of memory CD4+ T cell responses.

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“…Protective Antigen is a major component of the Anthrax Vaccine Adsorbed (AVA) (16,17). The vast majority of healthy subjects have had no exposure to this antigen.…”

Section: Introductionmentioning

confidence: 99%

Frequency of Epitope-Specific Naive CD4+ T Cells Correlates with Immunodominance in the Human Memory Repertoire

Kwok

Tan

Gillette

et al. 2012

The Journal of Immunology

107

120

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“…8 Since its initial licensure, more than two million individuals have received over eight million doses of AVA, and vaccination remains mandatory for all U.S. military personnel. 9,10 …”

Section: Introductionmentioning

confidence: 99%

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

et al. 2011

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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 IgG 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, 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 3 or 4 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 significantlylower 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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“…Anthrax can enter the human body through the intestines (ingestion), lungs (inhalation), and skin (cutaneous) and causes distinct clinical symptoms based on its site of entry. After the toxin enters the human body, the spores germinate into bacteria and secrete a toxin that causes local edema and, in systemic infections, cardiovascular collapse and death [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Insilico studies on anthrax lethal factor inhibitors: Pharmacophore modeling and virtual screening approaches towards designing of novel inhibitors for a killer

Roy¹,

Kumar²,

Machiraju³

et al. 2010

Journal of Molecular Graphics and Modelling

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The anthrax vaccine: No new tricks for an old dog

Cited by 14 publications

References 40 publications

Frequency of Epitope-Specific Naive CD4+ T Cells Correlates with Immunodominance in the Human Memory Repertoire

Frequency of Epitope-Specific Naive CD4+ T Cells Correlates with Immunodominance in the Human Memory Repertoire

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

Insilico studies on anthrax lethal factor inhibitors: Pharmacophore modeling and virtual screening approaches towards designing of novel inhibitors for a killer

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