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首页> 外文期刊>Vaccine >Reactogenicity and immunogenicity of live attenuated Salmonella enterica serovar Paratyphi A enteric fever vaccine candidates
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Reactogenicity and immunogenicity of live attenuated Salmonella enterica serovar Paratyphi A enteric fever vaccine candidates

机译：减毒肠炎沙门氏菌血清副伤寒A型肠热疫苗候选株的反应原性和免疫原性

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摘要

Eight Salmonella enterica serovar Paratyphi A strains were screened as candidates to create a live attenuated paratyphoid vaccine. Based on biochemical and phenotypic criteria, four strains, RKS2900. MGN9772, MGN9773 and MGN9779, were selected as progenitors for the construction of Delta phoPQ mutant derivatives. All strains were evaluated in vitro for auxotrophic phenotypes and sensitivity to deoxycholate and polymyxin B. All Delta phoPQ mutants were more sensitive to deoxycholate and polymyxin B than their wild-type progenitors, however MGN10028, MGN10044 and MGN10048, required exogenous purine for optimal growth. Purine requiring strains had acquired point mutations. in purB during strain construction. All four mutants were evaluated for reactogenicity and immunogenicity in an oral rabbit model. Three strains were reactogenic in a dose-dependent manner, while one strain, MGN10028, was well-tolerated at all doses administered. All Delta phoPQ strains were immunogenic following a single oral dose. The in vitro profile coupled with the favorable reactogenicity and immunogenicity profiles render MGN10028 a suitable live attenuated Paratyphi A vaccine candidate.
机译：筛选了八株肠炎沙门氏菌血清副伤寒A株作为候选疫苗，以制备减毒副伤寒活疫苗。根据生化和表型标准，四种菌株RKS2900。选择MGN9772，MGN9773和MGN9779作为祖细胞，以构建Delta phoPQ突变体衍生物。在体外评估了所有菌株的营养缺陷型和对脱氧胆酸和多粘菌素B的敏感性。所有Delta phoPQ突变体对脱氧胆酸和多粘菌素B的敏感性都比其野生型祖细胞高，但是MGN10028，MGN10044和MGN10048需要外源嘌呤以实现最佳生长。需要嘌呤的菌株已获得点突变。在菌株构建过程中的purB中。评价了这四个突变体在口服兔模型中的反应原性和免疫原性。 3株菌株具有剂量依赖性的致反应性，而1株MGN10028在所有剂量下均具有良好的耐受性。单次口服剂量后，所有Delta phoPQ菌株均具有免疫原性。体外谱以及良好的反应原性和免疫原性谱使MGN10028成为合适的减毒副伤寒活疫苗候选株。

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