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首页> 外文期刊>Infection and immunity >Safety of live oral Salmonella typhi vaccine strains with deletions in htrA and aroC aroD and immune response in humans.
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Safety of live oral Salmonella typhi vaccine strains with deletions in htrA and aroC aroD and immune response in humans.

机译：活的口服伤寒沙门氏菌疫苗菌株在htrA和aroC aroD缺失以及人类免疫反应中的安全性。

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A single-dose, oral Salmonella typhi vaccine strain has been sought as a carrier or vector of cloned genes encoding protective antigens of other pathogens. Such a hybrid vaccine, administered orally, would stimulate immune responses both at the mucosal surface and in the systemic compartment and would potentially provide protection against multiple pathogens. S. typhi CVD 908 and CVD 906, which harbor deletions in aroC and aroD, were further engineered by deletion in htrA to produce strains CVD 908-htrA and CVD 906-htrA, which are unable to sustain growth and are severely impaired in their ability to survive in host tissues. These strains were fed to humans at doses of 5 x 10(7) to 5 x 10(9) CFU with buffer, and safety and immune responses were assessed. CVD 908-htrA and CVD 906-htrA were well tolerated in volunteers; mild diarrhea in 3 of 36 volunteers and mild fever in 1 volunteer were the only notable adverse responses. The vaccine strains were not detected in blood cultures and only transiently detected in stool. Serum immune responses to S. typhi lipopolysaccharide and H antigens were observed in 75 to 100% of volunteers who received 5 x 10(8) to 5 x 10(9) CFU, and cells secreting S. typhi-specific antibodies were found in all volunteers after ingestion of either strain. Sixty-three percent to 83% of volunteers developed lymphoproliferative responses to S. typhi flagellar and particulate antigens after the higher doses. These studies demonstrate the potential of CVD 908-htrA as a live vector for the delivery of heterologous genes, and a clinical trial of such a construct is planned.
机译：已经寻求一种单剂量口服伤寒沙门氏菌疫苗菌株作为编码其他病原体保护性抗原的克隆基因的载体或载体。口服施用的这种杂合疫苗将刺激粘膜表面和全身区室的免疫反应，并可能提供针对多种病原体的保护作用。携带aroC和aroD缺失的伤寒沙门氏菌CVD 908和CVD 906通过在htrA中缺失进行进一步工程改造，以产生无法维持生长并严重损害其能力的CVD 908-htrA和CVD 906-htrA菌株。在宿主组织中生存将这些菌株以5 x 10（7）至5 x 10（9）CFU的剂量用缓冲液喂养给人类，并评估安全性和免疫反应。志愿者对CVD 908-htrA和CVD 906-htrA的耐受性良好。仅有的明显不良反应是36名志愿者中的3名轻度腹泻和1名志愿者中的轻度发烧。在血液培养物中未检测到疫苗株，仅在粪便中瞬时检测到了疫苗株。在接受5 x 10（8）至5 x 10（9）CFU的志愿者中，有75％到100％的志愿者观察到了针对伤寒沙门氏菌脂多糖和H抗原的血清免疫反应，并且在所有受试者中都发现了分泌伤寒沙门氏菌特异性抗体的细胞。摄入任何一种菌株后的志愿者。较高剂量后，有63％至83％的志愿者对伤寒沙门氏菌鞭毛和颗粒抗原产生了淋巴增生反应。这些研究证明了CVD 908-htrA作为活载体传递异源基因的潜力，并计划进行这种构建物的临床试验。

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