Functional Analysis of
            <i>Bacillus anthracis</i>
            Protective Antigen by Using Neutralizing Monoclonal Antibodies

Brossier, Fabien; Levy, M; Landier, Annie; Lafaye, Pierre; Mock, Michèle

doi:10.1128/iai.72.11.6313-6317.2004

Cited by 88 publications

(97 citation statements)

References 36 publications

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“…The reactivities of the mouse sera (an average of five mice per group) with the PA peptides are summarized in Table 3. We identified four new linear B-cell epitopes in domains 1 and 2 and confirmed a previously identified epitope in domain 4 (3,8,9,22,46). Furthermore, we evaluated the reactivities to the peptides with our two previously characterized PA MAbs, 7.5G and 10F4 (35).…”

Section: Resultssupporting

confidence: 64%

“…Immunization with protein containing domains 2 to 4 or domain 4 was significantly less effective in eliciting high-titer or neutralizing antibody responses. The inability of the domain 4 recombinant protein to elicit a neutralizing antibody response is in contrast to the observation that many neutralizing MAbs bind to this domain (3,21,22). Some of the best-studied antibodies to domain 4 recognize conformational epitopes (8,41) that may require an intact three-dimensional protein to elicit a response.…”

Section: Discussionmentioning

confidence: 60%

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Immunogenicity of Bacillus anthracis Protective Antigen Domains and Efficacy of Elicited Antibody Responses Depend on Host Genetic Background

Abboud

Casadevall

2008

Clin Vaccine Immunol

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Section: Resultssupporting

confidence: 64%

Section: Discussionmentioning

confidence: 60%

Immunogenicity of Bacillus anthracis Protective Antigen Domains and Efficacy of Elicited Antibody Responses Depend on Host Genetic Background

Abboud

Casadevall

2008

Clin Vaccine Immunol

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“…PA alone is nontoxic and a critical (protective) level of serum antibodies to this protein confers immunity to inhalational and cutaneous anthrax in laboratory and wild animals. Some protection to mice and rats was shown by antibodies, mostly mAbs, to LF & EF but the contribution of antibodies to these two proteins to immunity to B. anthracis is an open question [7]. Limited evidence of protection by anti EF against challenge with anthrax toxin or with spores of non-capsulated B. anthracis strain Sterne was published recently [8].…”

Section: Introductionmentioning

confidence: 99%

Serum IgG antibody response to the protective antigen (PA) of Bacillus anthracis induced by anthrax vaccine adsorbed (AVA) among U.S. military personnel

Singer

Schneerson

Bautista

et al. 2008

Vaccine

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The seroconversion rates and geometric mean concentrations (GMC) of IgG anti-PA for stored sera from U.S. military personnel immunized 3, 4, and 6 times with the U.S. licensed anthrax vaccine adsorbed were studied. Anti-PA IgG concentrations were measured by ELISA. All 246 vaccinees had low but detectable pre-immunization anti-PA IgG (GMC 1.83μg/mL). Three doses elicited a GMC of 60 μg/mL and a seroconversion rate of 85.3%, four doses elicited a GMC of 157 μg/mL and 67.9% and the sixth of 277 μg/mL and 45.5% respectively. The forth dose elicited 100% seroconversion compared to the pre-immunization level. These results should facilitate comparison between different immunization schedules and new vaccines.

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“…Hence, anthrax presents a very good model for antidote design, and antitoxins that act upon the mechanism of action of the toxin (including toxin binding, assembly, translocation into target cells) have been developed 12,[24][25][26][27] . This suggests that intrinsic neutralizing epitopes exist within the toxin structural motif.…”

Section: Introductionmentioning

confidence: 99%

Selection and characterization of human antibodies neutralizing Bacillus anthracis toxin

Zhou

Carney

Janda

2008

Bioorganic & Medicinal Chemistry

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A less than adequate therapeutic plan for the treatment of anthrax in the 2001 bioterrorism attacks has highlighted the importance of developing alternative or complementary therapeutic approaches for biothreat agents. In these regards passive immunization possesses several important advantages over active vaccination and the use of antibiotics, as it can provide immediate protection against Bacillus anthracis. Herein, we report the selection and characterization of several human monoclonal neutralizing antibodies against the toxin of B. anthracis from a phage displayed human scFv library. In total fifteen clones were selected with distinct sequences and high specificity to protective antigen and thus were the subject of a series of both biophysical and cell-based cytotoxicity assays. From this panel of antibodies a set of neutralizing antibodies were identified, of which clone A8 recognizes the lethal (and/or edema) factor binding domain, and clone F1, G11 and G12 recognize the cellular receptor binding domain within protective antigen. It was noted that all clones distinguish a conformational epitope existing on the protective antigen; this steric relationship was uncovered using a sequential epitope mapping approach. For each neutralizing antibody, the kinetic constants were determined by surface plasmon resonance, while the potency of protection was established using a two-tier macrophage cytotoxicity assay. Among the neutralizing antibodies identified, clone F1 possessed the highest affinity to protective antigen, and provided superior protection from lethal toxin in the cell cytotoxicity assay. The data presented provides to the ever-growing arsenal of immunological and functional analysis of monoclonal antibodies to the exotoxins of anthrax. In addition it grants new candidates for the prophylaxis and therapeutic treatment against this toxin.

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Functional Analysis of Bacillus anthracis Protective Antigen by Using Neutralizing Monoclonal Antibodies

Cited by 88 publications

References 36 publications

Immunogenicity of Bacillus anthracis Protective Antigen Domains and Efficacy of Elicited Antibody Responses Depend on Host Genetic Background

Immunogenicity of Bacillus anthracis Protective Antigen Domains and Efficacy of Elicited Antibody Responses Depend on Host Genetic Background

Serum IgG antibody response to the protective antigen (PA) of Bacillus anthracis induced by anthrax vaccine adsorbed (AVA) among U.S. military personnel

Selection and characterization of human antibodies neutralizing Bacillus anthracis toxin

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