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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. Here we demonstrate that disrupting the<jats:italic>htrA<\/jats:italic>gene, encoding the chaperone\/protease HtrA (High Temperature Requirement A), in the virulent<jats:italic>Bacillus anthracis<\/jats:italic>Vollum strain results in significant virulence attenuation in guinea pigs, rabbits and mice, underlying the universality of the attenuated phenotype associated with<jats:italic>htrA<\/jats:italic>knockout. Accordingly,<jats:italic>htrA<\/jats:italic>disruption was implemented for the development of a Sterne-derived safe live vaccine compatible with human use. The novel<jats:italic>B. anthracis<\/jats:italic>Sterne\u0394<jats:italic>htrA<\/jats:italic>strain secretes functional anthrax toxins but is 10\u201310<jats:sup>4<\/jats:sup>-fold less virulent than the Sterne vaccine strain depending on animal model (mice, guinea pigs, or rabbits). In spite of this attenuation, double or even single immunization with Sterne\u0394<jats:italic>htr<\/jats:italic>A 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. The efficacy of the immune-protective response in guinea pigs was maintained for at least 50 weeks after a<jats:italic>single<\/jats:italic>immunization.<\/jats:p>","DOI":"10.1038\/srep18908","type":"journal-article","created":{"date-parts":[[2016,1,6]],"date-time":"2016-01-06T10:12:46Z","timestamp":1452075166000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Next-Generation Bacillus anthracis Live Attenuated Spore Vaccine Based on the htrA- (High Temperature Requirement A) Sterne Strain"],"prefix":"10.1038","volume":"6","author":[{"given":"Theodor","family":"Chitlaru","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ma\u2019ayan","family":"Israeli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erez","family":"Bar-Haim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uri","family":"Elia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahar","family":"Rotem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon","family":"Ehrlich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ofer","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avigdor","family":"Shafferman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,1,6]]},"reference":[{"key":"BFsrep18908_CR1","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1016\/j.mam.2009.08.001","volume":"30","author":"A Driks","year":"2009","unstructured":"Driks, A. 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