12/2/2023 0 Comments Stun spore immunization![]() ![]() These three proteins are encoded by genes located on pXO1, one of the two virulence plasmids naturally harboured by B. ![]() anthracis secretes Lethal Toxin (LT) and Edema Toxin (ET), which are composed of binary combinations of the three proteins Protective Antigen (PA), Lethal Factor (LF) and Edema Factor (EF). The lethality of anthrax results from the bacterial exotoxins as well as the remarkable ability of the bacteria to proliferate in the host. The most lethal manifestation of Bacillus anthracis infection is represented by the respiratory form of the disease: the inhaled spores are transported by alveolar macrophages and dendritic cells to lymph nodes where they germinate into fast growing vegetative bacilli 2. The efficacy of the immune-protective response in guinea pigs was maintained for at least 50 weeks after a single immunization. In spite of this attenuation, double or even single immunization with SterneΔ htrA spores elicits immune responses which target toxaemia and bacteremia resulting in protection from subcutaneous or respiratory lethal challenge with a virulent strain in guinea pigs and rabbits. anthracis SterneΔ htrA strain secretes functional anthrax toxins but is 10–10 4-fold less virulent than the Sterne vaccine strain depending on animal model (mice, guinea pigs, or rabbits). Accordingly, htrA disruption was implemented for the development of a Sterne-derived safe live vaccine compatible with human use. Here we demonstrate that disrupting the htrA gene, encoding the chaperone/protease HtrA (High Temperature Requirement A), in the virulent Bacillus anthracis Vollum strain results in significant virulence attenuation in guinea pigs, rabbits and mice, underlying the universality of the attenuated phenotype associated with htrA knockout. Live attenuated vaccines, such as the nonencapsulated Sterne strain, do not meet the safety standards mandated for human use in the Western world and are approved for veterinary purposes only. Anthrax is a lethal disease caused by the gram-positive spore-producing bacterium Bacillus anthracis. ![]()
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