Genetic immunization against anthrax

Galloway, Darrell R.; Liner, Adriane; Legutki, Joseph Barten; Mateczun, Alfred; Barnewall, Roy E.; Estep, James E.

doi:10.1016/j.vaccine.2003.09.043

Cited by 59 publications

(34 citation statements)

References 10 publications

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“…Several candidate vaccines based on rPA have been described [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] and have been shown to be highly protective against lethal aerosol or parenteral B. anthracis spore challenge.…”

Section: Introductionmentioning

confidence: 99%

Comparative vaccine efficacy of different isoforms of recombinant protective antigen against Bacillus anthracis spore challenge in rabbits

Ribot

Powell

Ivins

et al. 2006

Vaccine

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Section: Introductionmentioning

confidence: 99%

Comparative vaccine efficacy of different isoforms of recombinant protective antigen against Bacillus anthracis spore challenge in rabbits

Ribot

Powell

Ivins

et al. 2006

Vaccine

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“…Since 2001, when spores of B. anthracis sent through the U.S. mail resulted in infection in 22 individuals, including 5 fatal cases of inhalation anthrax, significant efforts have been directed toward reevaluating our preparedness for possible bioterrorist threats, including weaponized anthrax. This has included renewed efforts to more critically evaluate the anthrax vaccine currently approved in the United States, BioThrax, as well as continued development of new, alternative vaccines for anthrax (1)(2)(3)(4)(5)(6). We previously showed that immunization of rabbits with a multiple antigenic peptide (MAP), which display multiple copies of a target sequence extending from a branched lysine core, was capable of eliciting antibody specific for a linear determinant in the 2␤2-2␤3 loop, which mediated high-titer neutralization of lethal toxin (LeTx) in vitro (7,8) and protection of rabbits from a targeted aerosol challenge of 200 50% lethal doses (LD 50 ) of B. anthracis Ames strain in vivo (9).…”

mentioning

confidence: 99%

Recombinant Vaccine Displaying the Loop-Neutralizing Determinant from Protective Antigen Completely Protects Rabbits from Experimental Inhalation Anthrax

Oscherwitz¹,

Yu²,

Jacobs³

et al. 2013

Clin. Vaccine Immunol.

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We previously showed that a multiple antigenic peptide (MAP) vaccine displaying amino acids (aa) 304 to 319 from the 2␤2-2␤3 loop of protective antigen was capable of protecting rabbits from an aerosolized spore challenge with Bacillus anthracis Ames strain. Antibodies to this sequence, referred to as the loop-neutralizing determinant (LND), are highly potent at neutralizing lethal toxin yet are virtually absent in rabbit and human protective antigen (PA) antiserum. While the MAP vaccine was protective against anthrax, it contains a single heterologous helper T cell epitope which may be suboptimal for stimulating an outbred human population. We therefore engineered a recombinant vaccine (Rec-LND) containing two tandemly repeated copies of the LND fused to maltose binding protein, with enhanced immunogenicity resulting from the p38/P4 helper T cell epitope from Schistosoma mansoni. Rec-LND was found to be highly immunogenic in four major histocompatibility complex (MHC)-diverse strains of mice. All (7/7) rabbits immunized with Rec-LND developed high-titer antibody, 6 out of 7 developed neutralizing antibody, and all rabbits were protected from an aerosolized spore challenge of 193 50% lethal doses (LD 50 ) of the B. anthracis Ames strain. Survivor serum from Rec-LND-immunized rabbits revealed significantly increased neutralization titers and specific activity compared to prechallenge levels yet lacked PA or lethal factor (LF) antigenemia. Control rabbits immunized with PA, which were also completely protected, appeared sterilely immune, exhibiting significant declines in neutralization titer and specific activity compared to prechallenge levels. We conclude that Rec-LND may represent a prototype anthrax vaccine for use alone or potentially combined with PA-containing vaccines.

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“…Ongoing research is also focused on the design and testing of vaccines targeting antigens other than PA in an effort to broaden the breadth of immunity induced through vaccination (8,15,30,40). This was motivated in part by the realization, informed primarily by analysis of PA-specific monoclonal antibodies (MAbs) in mice and humans, that the antibody specificities responsible for LeTx neutralization may be limited to only a few dominant specificities (1,7,28,29,44).…”

mentioning

confidence: 99%

Synthetic Peptide Vaccine Targeting a Cryptic Neutralizing Epitope in Domain 2 ofBacillus anthracisProtective Antigen

Oscherwitz

Jacobs

et al. 2009

Infect Immun

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Current evidence suggests that protective antigen (PA)-based anthrax vaccines may elicit a narrow neutralizing antibody repertoire, and this may represent a vulnerability with PA-based vaccines. In an effort to identify neutralizing specificities which may complement those prevalent in PA antiserum, we evaluated whether sequences within the 2␤2-2␤3 loop of PA, which are apparent in the crystal structure of heptameric but not monomeric PA, might represent a target for an epitope-specific vaccine for anthrax and, further, whether antibodies to these sequences are induced in rabbits immunized with monomeric PA. We evaluated the immunogenicity in rabbits of a multiple antigenic peptide (MAP) displaying copies of amino acids (aa) 305 to 319 of this region. Overall, four out of six rabbits vaccinated with the MAP peptide in Freund's adjuvant developed high-titer, high-avidity antibody responses which cross-reacted with the immobilized peptide sequence comprising aa 305 to 319 and with PA, as determined by an enzyme-linked immunosorbent assay, and which displayed potent and durable neutralization of lethal toxin (LeTx) in vitro, with peak titers which were 452%, 100%, 67%, and 41% of the peak neutralization titers observed in positive-control rabbits immunized with PA. Importantly, analysis of sera from multiple cohorts of rabbits with high-titer immunity to PA demonstrated a virtual absence of this potent antibody specificity, and work by others suggests that this specificity may be present at only low levels in primate PA antiserum. These results highlight the potential importance of this immunologically cryptic neutralizing epitope from PA as a target for alternative and adjunctive vaccines for anthrax.

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Genetic immunization against anthrax

Cited by 59 publications

References 10 publications

Comparative vaccine efficacy of different isoforms of recombinant protective antigen against Bacillus anthracis spore challenge in rabbits

Comparative vaccine efficacy of different isoforms of recombinant protective antigen against Bacillus anthracis spore challenge in rabbits

Recombinant Vaccine Displaying the Loop-Neutralizing Determinant from Protective Antigen Completely Protects Rabbits from Experimental Inhalation Anthrax

Synthetic Peptide Vaccine Targeting a Cryptic Neutralizing Epitope in Domain 2 ofBacillus anthracisProtective Antigen

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