scholarly journals Immunization against anthrax with aromatic compound-dependent (Aro-) mutants of Bacillus anthracis and with recombinant strains of Bacillus subtilis that produce anthrax protective antigen.

1990 ◽  
Vol 58 (2) ◽  
pp. 303-308 ◽  
Author(s):  
B E Ivins ◽  
S L Welkos ◽  
G B Knudson ◽  
S F Little
Keyword(s):  
Bacillus Subtilis ◽  
Bacillus Anthracis ◽  
Aromatic Compound ◽  
Protective Antigen ◽  
Recombinant Strains ◽  
Anthrax Protective Antigen

scholarly journals Correlation between Lethal Toxin-Neutralizing Antibody Titers and Protection from Intranasal Challenge with Bacillus anthracis Ames Strain Spores in Mice after Transcutaneous Immunization with Recombinant Anthrax Protective Antigen

2006 ◽  
Vol 74 (1) ◽  
pp. 794-797 ◽  
Author(s):  
Kristina K. Peachman ◽  
Mangala Rao ◽  
Carl R. Alving ◽  
Robert Burge ◽  
Stephen H. Leppla ◽  
...  
Keyword(s):  
Bacillus Anthracis ◽  
Protective Antigen ◽  
Neutralizing Antibody ◽  
Lethal Toxin ◽  
Vaccine Strategy ◽  
Transcutaneous Immunization ◽  
Antibody Titers ◽  
Anthrax Protective Antigen ◽  
Ames Strain ◽  
Recombinant Protective Antigen

ABSTRACT Transcutaneous immunization of mice with recombinant protective antigen (rPA) of Bacillus anthracis resulted in significantly higher lethal toxin-neutralizing antibody titers than did intramuscular injection of alum-adsorbed rPA. Immunized mice were partially protected against intranasal challenge with 235,000 (10 50% lethal doses) Ames strain B. anthracis spores. A highly significant correlation was observed between toxin-neutralizing antibody titer and survival after challenge. Future experiments with rabbits and nonhuman primates should confirm the significance of protection by this vaccine strategy.

scholarly journals Vaccination against Anthrax with Attenuated Recombinant Strains of Bacillus anthracis That Produce Protective Antigen

1999 ◽  
Vol 67 (2) ◽  
pp. 562-567 ◽  
Author(s):  
John P. Barnard ◽  
Arthur M. Friedlander
Keyword(s):  
Bacillus Anthracis ◽  
Protective Antigen ◽  
Plasmid Stability ◽  
Protective Efficacy ◽  
Live Vaccines ◽  
Antibody Titers ◽  
Anthrax Protective Antigen ◽  
Anthrax Vaccines

ABSTRACT The protective efficacy of several live, recombinant anthrax vaccines given in a single-dose regimen was assessed with Hartley guinea pigs. These live vaccines were created by transforming ΔANR and ΔSterne, two nonencapsulated, nontoxinogenic strains of Bacillus anthracis, with four different recombinant plasmids that express the anthrax protective antigen (PA) protein to various degrees. This enabled us to assess the effect of the chromosomal background of the strain, as well as the amount of PA produced, on protective efficacy. There were no significant strain-related effects on PA production in vitro, plasmid stability in vivo, survival of the immunizing strain in the host, or protective efficacy of the immunizing infection. The protective efficacy of the live, recombinant anthrax vaccine strains correlated with the anti-PA antibody titers they elicited in vivo and the level of PA they produced in vitro.

scholarly journals Genetic Construction of Bacillus subtilis Recombinant Strain, Producing Anthrax Protective Antigen

2018 ◽  
Vol 2 (2) ◽  
pp. 51-60
Keyword(s):  
Bacillus Subtilis ◽  
Recombinant Strain ◽  
Protective Antigen ◽  
Shuttle Vector ◽  
Subtilis Strain ◽  
Anthrax Vaccine ◽  
Anthrax Protective Antigen ◽  
Recombinant Bacillus Subtilis ◽  
New Generation ◽  
Anthrax Vaccines

Anthrax is a serious infectious disease with high mortality. The epidemiological security depends on the vaccination of susceptible animals and population at risk. But many of the existing anthrax vaccine strains possess low levels of protective antigen production and high reactogenicity. One of the most promising trends in production of new generation of vaccines is the cloning of particular determinants of immunogenicity of anthrax microbe for the creation of highly effective producers of Bacillus anthracis protective antigen. The aim of the article is to present the results of the study on the construction of recombinant Bacillus subtilis strain, producing B.anthracis protective antigen, promising for use in chemical anthrax vaccines technology. The pHT43PA plasmid containing the gene pag, providing the synthesis of protective antigen of the anthrax microbe and functioning stably in the cells of the recombinant strain Amy21(pHT43РА) of B. subtilis, was constructed on the basis of the shuttle vector pHT43. It is found out during the research, that the microbial cells of the recombinant strain Amy21(pHT43РА) of B. subtilis provide the production of immunologically active protective antigen in quantities, not inferior than anthrax vaccine strains. These data, as well as safety and simplicity of В. subtilis make it possible to continue the research of this recombinant strain as a producer of anthrax protective antigen, promising for use in vaccines production

scholarly journals Secrening Producer of Truncated Bacillus anthracis Protective Antigen in Bacillus subtilis

2016 ◽  
Vol 10 (4) ◽  
pp. 2627-2632
Author(s):  
I K Biriukova ◽  
A B Shevelev ◽  
M V Zylkova ◽  
V N Trifan ◽  
A A Lebedeva ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Bacillus Anthracis ◽  
Protective Antigen

scholarly journals Use of a Promoter Trap System in Bacillus anthracis and Bacillus subtilis for the Development of Recombinant Protective Antigen-Based Vaccines

2003 ◽  
Vol 71 (2) ◽  
pp. 801-813 ◽  
Author(s):  
O. Gat ◽  
I. Inbar ◽  
R. Aloni-Grinstein ◽  
E. Zahavy ◽  
C. Kronman ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Bacillus Anthracis ◽  
Protective Antigen ◽  
Expression Plasmid ◽  
Secretion Stress ◽  
Trap System ◽  
Promoter Trap ◽  
Ability To Drive ◽  
Practical Implications ◽  
Recombinant Protective Antigen

ABSTRACT We have recently reported Bacillus anthracis attenuated live vaccine strains efficiently expressing recombinant protective antigen (rPA) and have shown a direct correlation between the level of rPA secreted by these cells and efficacy (S. Cohen, I. Mendelson, Z. Altboum, D. Kobiler, E. Elhanany, T. Bino, M. Leitner, I. Inbar, H. Rosenberg, Y. Gozes, R. Barak, M. Fisher, C. Kronman, B. Velan, and A. Shafferman, Infect. Immun. 68:4549-4558, 2000). To isolate more potent Bacillus promoters for a further increase in the production of rPA, we developed a promoter trap system based on various gfp reporter genes adapted for use in both Bacillus subtilis and B. anthracis backgrounds. Accordingly, a B. anthracis library of 6,000 clones harboring plasmids with chromosomal B. anthracis DNA fragments inserted upstream from gfpuv was constructed. Based on fluorescence intensity, 57 clones carrying potentially strong promoters were identified, some of which were DNA sequenced. The most potent B. anthracis promoter identified (Pntr; 271 bp) was 500 times more potent than the native pagA promoter and 70 times more potent than the α-amylase promoter (Pamy). This very potent promoter was tested along with the other promoters (which are three, six, and eight times more potent than Pamy) for the ability to drive expression of rPA in either B. subtilis or B. anthracis. The number of cell-associated pre-PA molecules in B. anthracis was found to correlate well with the strength of the promoter. However, there appeared to be an upper limit to the amount of mature PA secreted into the medium, which did not exceed that driven by Pamy. Furthermore, the rPA constructs fused to the very potent promoters proved to be deleterious to the bacterial hosts and consequently led to genetic instability of the PA expression plasmid. Immunization with attenuated B. anthracis expressing rPA under the control of promoters more potent than Pamy was less efficient in eliciting anti-PA antibodies than that attained with Pamy. The results are consistent with the notion that overexpression of PA leads to severe secretion stress and have practical implications for the design of second-generation rPA-based vaccines.

scholarly journals A High-Affinity Monoclonal Antibody to Anthrax Protective Antigen Passively Protects Rabbits before and after Aerosolized Bacillus anthracis Spore Challenge

2005 ◽  
Vol 73 (2) ◽  
pp. 795-802 ◽  
Author(s):  
Nehal Mohamed ◽  
Michelle Clagett ◽  
Juan Li ◽  
Steven Jones ◽  
Steven Pincus ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bacillus Anthracis ◽  
Protective Antigen ◽  
Lethal Dose ◽  
Cell Binding ◽  
Anthrax Spore ◽  
Before And After ◽  
Anthrax Infection ◽  
Anthrax Protective Antigen ◽  
Binding Component

ABSTRACT We have developed a therapeutic for the treatment of anthrax using an affinity-enhanced monoclonal antibody (ETI-204) to protective antigen (PA), which is the central cell-binding component of the anthrax exotoxins. ETI-204 administered preexposure by a single intravenous injection of a dose of between 2.5 and 10 mg per animal significantly protected rabbits from a lethal aerosolized anthrax spore challenge (∼60 to 450 times the 50% lethal dose of Bacillus anthracis Ames). Against a similar challenge, ETI-204 administered intramuscularly at a 20-mg dose per animal completely protected rabbits from death (100% survival). In the postexposure setting, intravenous administration of ETI-204 provided protection 24 h (8 of 10) and 36 h (5 of 10) after spore challenge. Administration at 48 h postchallenge, when 3 of 10 animals had already succumbed to anthrax infection, resulted in the survival of 3 of 7 animals (43%) for the duration of the study (28 days). Importantly, surviving ETI-204-treated animals were free of bacteremia by day 10 and remained so until the end of the studies. Only 11 of 51 ETI-204-treated rabbits had positive lung cultures at the end of the studies. Also, rabbits that were protected from inhalational anthrax by administration of ETI-204 developed significant titers of PA-specific antibodies. Presently, the sole therapeutic regimen available to treat infection by inhalation of B. anthracis spores is a 60-day course of antibiotics that is effective only if administered prior to or shortly after exposure. Based upon results reported here, ETI-204 is an effective therapy for prevention and treatment of inhalational anthrax.

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