Monitoring of ELISA-reactive antibodies against anthrax protective antigen (PA), lethal factor (LF), and toxin-neutralising antibodies in serum of individuals vaccinated against anthrax with the PA-based UK anthrax vaccine

Grunow, Roland; Porsch-Özçürümez, Mustafa; Splettstoesser, Wolf D.; Buckendahl, A.; Hahn, Ulrike; Beyer, Wolfgang; Böhm, Reinhard; Huber, Maria; Esche, Ulrich vd; Bessler, Wolfgang G.; Frangoulidis, Dimitrios; Finke, Ernst-Jürgen

doi:10.1016/j.vaccine.2007.01.056

Cited by 26 publications

(17 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An indirect enzyme-linked immunosorbent assay (ELISA) for the detection and quantification of lethal factor was adapted from past studies (32)(33)(34). Serum samples from control and infected A/J mice were normalized to 3 mg/ml total protein of bovine serum albumin (BSA) by a Bradford assay.…”

Section: Mouse Infectionsmentioning

confidence: 99%

Global Metabolomic Analysis of a Mammalian Host Infected with Bacillus anthracis

2015

View full text Add to dashboard Cite

bWhereas DNA provides the information to design life and proteins provide the materials to construct it, the metabolome can be viewed as the physiology that powers it. As such, metabolomics, the field charged with the study of the dynamic small-molecule fluctuations that occur in response to changing biology, is now being used to study the basis of disease. Here, we describe a comprehensive metabolomic analysis of a systemic bacterial infection using Bacillus anthracis, the etiological agent of anthrax disease, as the model pathogen. An organ and blood analysis identified approximately 400 metabolites, including several key classes of lipids involved in inflammation, as being suppressed by B. anthracis. Metabolite changes were detected as early as 1 day postinfection, well before the onset of disease or the spread of bacteria to organs, which testifies to the sensitivity of this methodology. Functional studies using pharmacologic inhibition of host phospholipases support the idea of a role of these key enzymes and lipid mediators in host survival during anthrax disease. Finally, the results are integrated to provide a comprehensive picture of how B. anthracis alters host physiology. Collectively, the results of this study provide a blueprint for using metabolomics as a platform to identify and study novel host-pathogen interactions that shape the outcome of an infection. Metabolomics, a quickly emerging "omics" field in systems biology, is the global analysis of small molecules in a biological sample (1). Since the 1950s, the central dogma of biological information has been the transition from genes to transcript to protein (2). Only recently has the use of high-throughput systems biology been used to study the products of protein activity, the metabolites. The metabolome represents all endogenous and exogenous low-molecular-mass (Ͻ1-kDa) molecules present in a biological state, providing an instantaneous "snapshot" of the cell's metabolic and physiological activity (3). Applications of global metabolomic analysis fall into three broad categories: (i) disease diagnosis, (ii) biomarker and drug discovery, and (iii) study of metabolic pathways and their perturbations due to external factors (1). The analysis of altered metabolites has the potential for discovery of new biomarkers, thus providing the possibility of earlier intervention and insights into the mechanisms of diseases (4).The diagnosis of a bacterial infection encompasses an assessment of clinical symptoms, positive culture of an organism from tissues or blood, and/or reliance on often expensive, outsourced molecular methods (5). Metabolomics provides a unique perspective on bacterial infections as it is able to comprehensively characterize a vast number of metabolic changes in response to a biological perturbation within the host (2). In addition to the potential for biomarker discovery, the metabolic profiles obtained from this analysis can give insight into the identity and nature of molecules involved in the immune response, detect alterations in ho...

show abstract

Section: Mouse Infectionsmentioning

confidence: 99%

Global Metabolomic Analysis of a Mammalian Host Infected with Bacillus anthracis

2015

View full text Add to dashboard Cite

show abstract

“…Experiments with animal models indicated that induction of neutralization antibody directed against PA in the host is correlated with protective immunity (3,5,15,20,25,26). Although there are many studies of humoral responses against PA after vaccination in humans (2,8,9,13,19), studies of cellular responses against PA after AVA vaccination are quite limited (1,12,24). In general, cellular responses elicited by vaccines are not well characterized, due to difficulties in monitoring of cellular immune responses.…”

mentioning

confidence: 99%

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

et al. 2008

View full text Add to dashboard Cite

“…In order to produce human PA and LF specific monoclonal antibodies we used peripheral blood lymphocytes (PBLs) from persons vaccinated with the UK anthrax vaccine. First, we screened the sera of the donors by ELISA for toxin-specific antibodies, and in a cellular neutralization assay for protective activity (Grunow et al 2007). From the ELISA results listed in Table 1 we conclude that at least three immunizations are needed to induce a significant level of PA-and LF-specific serum antibody titers.…”

Section: Resultsmentioning

confidence: 99%

Passive vaccination with a human monoclonal antibody: Generation of antibodies and studies for efficacy in Bacillus anthracis infections

et al. 2011

Self Cite

View full text Add to dashboard Cite

Monitoring of ELISA-reactive antibodies against anthrax protective antigen (PA), lethal factor (LF), and toxin-neutralising antibodies in serum of individuals vaccinated against anthrax with the PA-based UK anthrax vaccine

Cited by 26 publications

References 28 publications

Global Metabolomic Analysis of a Mammalian Host Infected with Bacillus anthracis

Global Metabolomic Analysis of a Mammalian Host Infected with Bacillus anthracis

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

Passive vaccination with a human monoclonal antibody: Generation of antibodies and studies for efficacy in Bacillus anthracis infections

Contact Info

Product

Resources

About

Monitoring of ELISA-reactive antibodies against anthrax protective antigen (PA), lethal factor (LF), and toxin-neutralising antibodies in serum of individuals vaccinated against anthrax with the PA-based UK anthrax vaccine

Cited by 26 publications

References 28 publications

Global Metabolomic Analysis of a Mammalian Host Infected with Bacillus anthracis

Global Metabolomic Analysis of a Mammalian Host Infected with Bacillus anthracis

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

Passive vaccination with a human monoclonal antibody: Generation of antibodies and studies for efficacy in Bacillus anthracis infections

Contact Info

Product

Resources

About

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