Antibody Responses to a Spore Carbohydrate Antigen as a Marker of Nonfatal Inhalation Anthrax in Rhesus Macaques

Saile, Elke; Boons, Geert‐Jan; Buskas, Therese; Carlson, Russell W.; Kannenberg, Elmar L.; Barr, John R.; Boyer, Anne; Gallegos-Candela, Maribel; Quinn, Conrad P.

doi:10.1128/cvi.00475-10

Cited by 16 publications

(8 citation statements)

References 34 publications

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“…Although it was somewhat unexpected that these animals did not succumb to anthrax, the results suggest that inhalational anthrax is not 100% lethal in the cynomolgus macaque inhalational anthrax model, which is consistent with two rhesus macaque inhalational anthrax studies (11,22). Moreover, it can be speculated that an early robust neutrophil response, followed by a marked total WBC response (including lymphocytes), might have been adequate to promote survival for these two untreated control animals.…”

Section: Discussionsupporting

confidence: 71%

Development of an Inhalational Bacillus anthracis Exposure Therapeutic Model in Cynomolgus Macaques

Henning

Comer

Stark

et al. 2012

Clin. Vaccine Immunol.

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Appropriate animal models are required to test medical countermeasures to bioterrorist threats. To that end, we characterized a nonhuman primate (NHP) inhalational anthrax therapeutic model for use in testing anthrax therapeutic medical countermeasures according to the U.S. Food and Drug Administration Animal Rule. A clinical profile was recorded for each NHP exposed to a lethal dose of Bacillus anthracis Ames spores. Specific diagnostic parameters were detected relatively early in disease progression, i.e., by blood culture (ϳ37 h postchallenge) and the presence of circulating protective antigen (PA) detected by electrochemiluminescence (ECL) ϳ38 h postchallenge, whereas nonspecific clinical signs of disease, i.e., changes in body temperature, hematologic parameters (ca. 52 to 66 h), and clinical observations, were delayed. To determine whether the presentation of antigenemia (PA in the blood) was an appropriate trigger for therapeutic intervention, a monoclonal antibody specific for PA was administered to 12 additional animals after the circulating levels of PA were detected by ECL. Seventy-five percent of the monoclonal antibody-treated animals survived compared to 17% of the untreated controls, suggesting that intervention at the onset of antigenemia is an appropriate treatment trigger for this model. Moreover, the onset of antigenemia correlated with bacteremia, and NHPs were treated in a therapeutic manner. Interestingly, brain lesions were observed by histopathology in the treated nonsurviving animals, whereas this observation was absent from 90% of the nonsurviving untreated animals. Our results support the use of the cynomolgus macaque as an appropriate therapeutic animal model for assessing the efficacy of medical countermeasures developed against anthrax when administered after a confirmation of infection. Bacillus anthracis is a Gram-positive, rod-shaped, aerobic and/or facultative anaerobic, spore-forming bacterium that can cause human disease via the gastrointestinal, cutaneous, or inhalation (pulmonary) routes, each resulting in different clinical manifestations of disease (4,20). The pulmonary form of B. anthracis is the most lethal, and the incubation period usually varies from 1 to 6 days, depending upon the dose received (5). After inhalation exposure, some reports suggest a delayed onset of several weeks in low-dose exposure or after the removal of therapeutic intervention (4). In inhalation anthrax, the initial clinical signs and symptoms are nonspecific and may include malaise, headache, fever, nausea, and vomiting (4). These are followed by a sudden onset of respiratory distress with dyspnea, stridor, cyanosis, and chest pain. The onset of respiratory distress is followed by shock and often death, with close to 100% mortality in untreated cases (4).The mortality caused by B. anthracis is predominantly due to the three well-characterized virulence factors: the capsule and two toxins (23). The polyglutamate capsule prevents phagocytosis of the bacterium. Three polypeptides-protective antigen...

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Section: Discussionsupporting

confidence: 71%

Development of an Inhalational Bacillus anthracis Exposure Therapeutic Model in Cynomolgus Macaques

Henning

Comer

Stark

et al. 2012

Clin. Vaccine Immunol.

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“…These mAbs were used to set up a new capture assay for the detection of spores in complex samples. Interestingly, a specific antibody response against the anthrose-containing trisaccharide conjugated to mcKLH and particularly to the anthrosyl moiety was induced in rhesus macaques exposed to virulent aerosolized B. anthracis Ames spores [81]. Five animals were infected with spores and developed bacteremia and toxemia consistent with infection.…”

Section: Immune Response Against the Conjugated Tetrasaccharidementioning

confidence: 98%

Glycan surface antigens fromBacillus anthracisas vaccine targets: current status and future perspectives

Adamo

2014

Expert Review of Vaccines

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Over recent years great attention has been directed to the discovery of novel antigens from Bacillus anthracis, because of the potential of its spores in the development of weapons for mass destruction. Substantial effort has been directed to the identification and immunochemical evaluation of glycans that might be used for specific diagnostic detection of the spores or immune-mediated prevention of anthrax. Carbohydrate structures found on surfaces of vegetative cells and spores are herein discussed. Among them, the cell wall polysaccharide and the tetrasaccharide unit isolated from the exosporium protein BclA were proven immunogenic in an animal model after covalent linkage to carrier protein. Further investigation is needed to fully assess the potential of these promising carbohydrate antigens for vaccine development.

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“…Although they are not strictly specific for B. anthracis spores, it has been argued that antibodies against anthrose-containing saccharides may still have potential as immuno-capturing components for a sensitive spore detection system (6,26,27). Additionally, antibody responses to the anthrose-containing oligosaccharide may have diagnostic value in confirming aerosol exposure to B. anthracis spores (18).…”

mentioning

confidence: 99%

Identification of an African Bacillus anthracis Lineage That Lacks Expression of the Spore Surface-Associated Anthrose-Containing Oligosaccharide

Tamborrini¹,

Bauer²,

Bolz³

et al. 2011

Journal of Bacteriology

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Antibody Responses to a Spore Carbohydrate Antigen as a Marker of Nonfatal Inhalation Anthrax in Rhesus Macaques

Cited by 16 publications

References 34 publications

Development of an Inhalational Bacillus anthracis Exposure Therapeutic Model in Cynomolgus Macaques

Development of an Inhalational Bacillus anthracis Exposure Therapeutic Model in Cynomolgus Macaques

Glycan surface antigens fromBacillus anthracisas vaccine targets: current status and future perspectives

Identification of an African Bacillus anthracis Lineage That Lacks Expression of the Spore Surface-Associated Anthrose-Containing Oligosaccharide

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