The Anthrax Vaccine Adsorbed Vaccine Generates Protective Antigen (PA)-Specific CD4
            <sup>+</sup>
            T Cells with a Phenotype Distinct from That of Naïve PA T Cells

Kwok, William W.; Yang, Junbao; James, Eddie A.; Bui, John; Huston, Laurie; Wiesen, Andrew R.; Roti, Michelle

doi:10.1128/iai.00324-08

Cited by 31 publications

(30 citation statements)

References 29 publications

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“…Previous studies in humans showed that AVA stimulated the production of CD4 ϩ T cells that recognized multiple epitopes within PA and that these responses were detected in vaccinated and, surprisingly, also in nonvaccinated subjects (18,19). The frequencies of PA-specific T cells were higher in vaccinees than in nonvaccinees.…”

Section: Discussionmentioning

confidence: 81%

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

Quinn¹,

Sabourin²,

Niemuth³

et al. 2012

Clin. Vaccine Immunol.

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05). PA-specific gamma interferon (IFN-␥) and interleukin-4 (IL-4) CD4؉ cell frequencies and T cell stimulation indices were sustained through 50.5 months (the last time point measured). PA-specific memory B cell frequencies were highly variable but, in general, were detectable in peripheral blood mononuclear cells (PBMC) by 2 months, were significantly above control levels by 7 months, and remained detectable in the HuAVA and 1:5 and 1:20 AVA groups through 42 months (the last time point measured). HuAVA and diluted AVA elicited a combined Th1/Th2 response and robust immunological priming, with sustained production of high-avidity PA-specific functional antibody, long-term immune cell competence, and immunological memory (30 months for 1:20 AVA and 52 months for 1:10 AVA). Vaccinated animals surviving inhalation anthrax developed high-magnitude anamnestic anti-PA IgG and TNA responses.

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Section: Discussionmentioning

confidence: 81%

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

Quinn¹,

Sabourin²,

Niemuth³

et al. 2012

Clin. Vaccine Immunol.

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“…The possible use of PA-derived epitopes for DRB1*04:01 and DRB1*07:01 and class II tetramers as tools to examine PA-specific Th2 CD4 ϩ cellular immune responses in AVA vaccinees was recently illustrated (28). This is of great interest in light of the potential use of HLA tetramers as tools to monitor T cell responses in vaccinated individuals and for design of subunit and peptide vaccine candidates against B. anthracis and other pathogens (29,30).…”

Section: Discussionmentioning

confidence: 99%

Human Leukocyte Antigens and Cellular Immune Responses to Anthrax Vaccine Adsorbed

et al. 2013

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. 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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“…PA immunization leads to Th-dependent Ab responses (15,25). Th cells utilize cytokine-and CD154-dependent mechanisms to drive the differentiation of B cells into Ab-secreting cells via cytokine receptor and CD40 signaling, respectively (23).…”

Section: Discussionmentioning

confidence: 99%

CD1d-Dependent B-Cell Help by NK-Like T Cells Leads to Enhanced and Sustained Production of Bacillus anthracis Lethal Toxin-Neutralizing Antibodies

et al. 2010

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The current Bacillus anthracis vaccine consists largely of protective antigen (PA), the protein of anthrax toxin that mediates entry of edema factor (EF) or lethal factor (LF) into cells. PA induces protective antibody (Ab)-mediated immunity against Bacillus anthracis but has limited efficacy and duration. We previously demonstrated that activation of CD1d-restricted natural killer-like T cells (NKT) with a CD1d-binding glycolipid led to enhanced Ab titers specific for foreign antigen (Ag). We therefore tested the hypothesis that activation of NKT cells with the CD1d ligand (␣-galactosylceramide [␣-GC]) at the time of immunization improves PA-specific Ab responses. We observed that ␣-GC enhanced PA-specific Ab titers in C57BL/6 mice. In CD1d ؊/؊ mice deficient in type I and type II NKT cells the anti-PA Ab response was diminished. In J␣281 ؊/؊ mice expressing CD1d but lacking type I ␣-GC-reactive NKT cells, ␣-GC did not enhance the Ab response. In vitro neutralization assays were performed and showed that the Ab titers correlated with protection of macrophages against anthrax lethal toxin (LT). The neutralization capacity of the Ab was further tested in lethal challenge studies, which revealed that NKT activation leads to enhanced in vivo protection against LT. Anti-PA Ab titers, neutralization, and protection were then measured over a period of several months, and this revealed that NKT activation leads to a sustained protective Ab response. These results suggest that NKT-activating CD1d ligands could be exploited for the development of improved vaccines for Bacillus anthracis that increase not only neutralizing Ab titers but also the duration of the protection afforded by Ab.

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The Anthrax Vaccine Adsorbed Vaccine Generates Protective Antigen (PA)-Specific CD4 ⁺ T Cells with a Phenotype Distinct from That of Naïve PA T Cells

Cited by 31 publications

References 29 publications

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

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

Human Leukocyte Antigens and Cellular Immune Responses to Anthrax Vaccine Adsorbed

CD1d-Dependent B-Cell Help by NK-Like T Cells Leads to Enhanced and Sustained Production of Bacillus anthracis Lethal Toxin-Neutralizing Antibodies

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The Anthrax Vaccine Adsorbed Vaccine Generates Protective Antigen (PA)-Specific CD4 + T Cells with a Phenotype Distinct from That of Naïve PA T Cells

Cited by 31 publications

References 29 publications

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

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

Human Leukocyte Antigens and Cellular Immune Responses to Anthrax Vaccine Adsorbed

CD1d-Dependent B-Cell Help by NK-Like T Cells Leads to Enhanced and Sustained Production of Bacillus anthracis Lethal Toxin-Neutralizing Antibodies

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The Anthrax Vaccine Adsorbed Vaccine Generates Protective Antigen (PA)-Specific CD4 ⁺ T Cells with a Phenotype Distinct from That of Naïve PA T Cells