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Anthrax vaccine recipients lack antibody against the loop neutralizing determinant: A protective neutralizing epitope from Bacillus anthracis protective antigen.

ABSTRACT: Epitope-focused immunogens can elicit antibody against the loop neutralizing determinant (LND), a neutralizing epitope found within the 2?2-2?3 loop of protective antigen (PA), which can protect rabbits from high-dose inhalation challenge with Bacillus anthracis Ames strain. Interestingly, data suggests that this epitope is relatively immunosilent in rabbits and non-human primates immunized with full length PA.To determine whether the LND is immunosilent among humans vaccinated with PA, we screened antisera from AVA- or placebo-vaccinees from a clinical trial for antibody reactive with the LND.AVA-vaccinee sera had significant PA-specific antibody compared to placebo-vaccinee sera; however, sera from the two cohorts were indistinguishable with regard to the frequency of individuals with antibody specific for the LND.AVA-vaccinees have a low frequency of antibody reactive with the LND. As with rabbits and non-human primates, the elicitation of LND-specific antibody in humans appears to require immunization with an epitope-focused vaccine.

SUBMITTER: Oscherwitz J

PROVIDER: S-EPMC4519083 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Anthrax vaccine recipients lack antibody against the loop neutralizing determinant: A protective neutralizing epitope from Bacillus anthracis protective antigen.

Oscherwitz Jon J Quinn Conrad P CP Cease Kemp B KB

Vaccine 20150326 20

<h4>Background</h4>Epitope-focused immunogens can elicit antibody against the loop neutralizing determinant (LND), a neutralizing epitope found within the 2β2-2β3 loop of protective antigen (PA), which can protect rabbits from high-dose inhalation challenge with Bacillus anthracis Ames strain. Interestingly, data suggests that this epitope is relatively immunosilent in rabbits and non-human primates immunized with full length PA.<h4>Methods</h4>To determine whether the LND is immunosilent among ...[more]

PMID: 25820066

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Project description:BACKGROUND:Bacillus cereus biovar anthracis (Bcbva) is an emergent bacterium closely related to Bacillus anthracis, the etiological agent of anthrax. The latter has a worldwide distribution and usually causes infectious disease in mammals associated with savanna ecosystems. Bcbva was identified in humid tropical forests of Côte d'Ivoire in 2001. Here, we characterize the potential geographic distributions of Bcbva in West Africa and B. anthracis in sub-Saharan Africa using an ecological niche modeling approach. METHODOLOGY/PRINCIPAL FINDINGS:Georeferenced occurrence data for B. anthracis and Bcbva were obtained from public data repositories and the scientific literature. Combinations of temperature, humidity, vegetation greenness, and soils values served as environmental variables in model calibrations. To predict the potential distribution of suitable environments for each pathogen across the study region, parameter values derived from the median of 10 replicates of the best-performing model for each pathogen were used. We found suitable environments predicted for B. anthracis across areas of confirmed and suspected anthrax activity in sub-Saharan Africa, including an east-west corridor from Ethiopia to Sierra Leone in the Sahel region and multiple areas in eastern, central, and southern Africa. The study area for Bcbva was restricted to West and Central Africa to reflect areas that have likely been accessible to Bcbva by dispersal. Model predicted values indicated potential suitable environments within humid forested environments. Background similarity tests in geographic space indicated statistical support to reject the null hypothesis of similarity when comparing environments associated with B. anthracis to those of Bcbva and when comparing humidity values and soils values individually. We failed to reject the null hypothesis of similarity when comparing environments associated with Bcbva to those of B. anthracis, suggesting that additional investigation is needed to provide a more robust characterization of the Bcbva niche. CONCLUSIONS/SIGNIFICANCE:This study represents the first time that the environmental and geographic distribution of Bcbva has been mapped. We document likely differences in ecological niche-and consequently in geographic distribution-between Bcbva and typical B. anthracis, and areas of possible co-occurrence between the two. We provide information crucial to guiding and improving monitoring efforts focused on these pathogens.

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Anthrax vaccine recipients lack antibody against the loop neutralizing determinant: A protective neutralizing epitope from Bacillus anthracis protective antigen.

Publications

Anthrax vaccine recipients lack antibody against the loop neutralizing determinant: A protective neutralizing epitope from Bacillus anthracis protective antigen.

Similar Datasets

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