Protective activity and immunogenicity of two recombinant anthrax vaccines for veterinary use.
ABSTRACT In this study, the efficacy of two experimental vaccines against Bacillus anthracis toxinaemia was evaluated in the rabbit model. A recombinant Protective Antigen (rPA) mutant and a trivalent vaccine (TV) composed by the rPA, a inactive mutant of Lethal Factor (mLF-Y728A; E735A) and a inactive mutant of Edema Factor (mEF-K346R), both emulsified with mineral oils, were evaluated for their immunogenicity and protective activity in New Zealand white rabbits. Rabbits vaccinated subcutaneously with rPA and TV rapidly produced high level of anti-PA, anti-LF and anti-EF antibodies, which were still present 6 months later. In the efficacy test, these vaccines protected 100% of rabbits challenged with B. anthracis virulent strain 0843 one week after the vaccination. Moreover, all animals vaccinated twice with rPA and TV, resisted B. anthracis infection 6 months later. Our data indicate that rPA and TV could be good vaccine candidates for inducing protection against B. anthracis infection in target animal host. They could successfully be used in an emergency with simultaneous long-acting antibiotics to halt incubating infections or during an anthrax epidemic.
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ABSTRACT: 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.Expert Review of Vaccines 05/2014; DOI:10.1586/14760584.2014.924404 · 4.22 Impact Factor
Chapter: Anthrax VaccinesBacillus anthracis and Anthrax, 11/2010: pages 269 - 293; , ISBN: 9780470891193
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ABSTRACT: Effective measures for the prophylaxis and treatment of anthrax are still required for counteracting the threat posed by inhalation anthrax. In this study, we first demonstrated that the chimeric protein LFn-PA, created by fusing the protective antigen (PA)-binding domain of lethal factor (LFn) to PA, retained the functions of the respective molecules. On the basis of this observation, we attempted to develop an antitoxin that targets the binding of lethal factor (LF) and/or edema factor (EF) to PA and the transportation of LF/EF. Therefore, we replaced PA in LFn-PA with a dominant-negative inhibitory PA (DPA), i.e., PA(F427D). In in vitro models of anthrax intoxication, the LFn-DPA chimera showed 3-fold and 2-fold higher potencies than DPA in protecting sensitive cells against anthrax lethal toxin (LeTx) and edema toxin (EdTx), respectively. In animal models, LFn-DPA exhibited strong potency in rescuing mice from lethal challenge with LeTx. We also evaluated the immunogenicity and immunoprotective efficacy of LFn-DPA as an anthrax vaccine candidate. In comparison with recombinant PA, LFn-DPA induced significantly higher levels of the anti-PA immune response. Moreover, LFn-DPA elicited an anti-LF antibody response that could cross-react with EF. Mice immunized with LFn-DPA tolerated a LeTx challenge that was 5 times its 50% lethal dose. Thus, LFn-DPA represents a highly effective trivalent vaccine candidate for both preexposure and postexposure vaccination. Overall, we have developed a novel and dually functional reagent for the prophylaxis and treatment of anthrax.Antimicrobial Agents and Chemotherapy 11/2010; 54(11):4750-7. DOI:10.1128/AAC.00640-10 · 4.57 Impact Factor