Phase I clinical trials of aroA aroD and aroA aroD htrA attenuated S-typhi vaccines;: effect of formulation on safety and immunogenicity
Phase I clinical trials of aroA aroD and aroA aroD htrA attenuated S-typhi vaccines;: effect of formulation on safety and immunogenicity
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DOI：
10.1016/s0264-410x(99)00424-7
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发表时间：
2000-02-14
期刊：
影响因子：
5.5
通讯作者：
Lindberg, AA
中科院分区：
文献类型：
--
作者：
Dilts, DA;Riesenfeld-Örn, I;Lindberg, AA
PBCC211 是伤寒沙门氏菌 CDC10 80 菌株的 aroA aroD 衍生物，在 I 期试验中作为单剂量伤寒疫苗进行了测试。三种不同的疫苗制剂，重组冻干细菌。总共 86 名成年志愿者口服新鲜生长的细菌或从袋中重组的冻干细菌。还在 38 名志愿者中测试了 aroA aroD Arl A 菌株 PBCC222。配方影响安全和免疫原剂量的确定；重建的冻干培养物需要比肉汤培养物更高的剂量来刺激血清转化。一般而言，无论减毒或配制如何，使大多数组成员发生血清转化的剂量都会产生不良症状。在这些aroA aroD 或aroA aroD htrA 菌株中，无法将症状的存在与实现显着的免疫原性分开，这妨碍了它们在测试的制剂中用作单剂量伤寒疫苗。这些菌株在较低、安全水平下的多次剂量可能作为外来抗原的载体是有效的，(C) 2000 Elsevier Science Ltd。保留所有权利。
PBCC211, an aroA aroD derivative of S. typhi strain CDC10 80, was tested in phase I trials as a single dose typhoid fever vaccine. Three different vaccine preparations, reconstituted lyophilized bacteria. freshly grown bacteria or lyophilized bacteria reconstituted from sachets, were orally administered to a total of 86 adult volunteers. An aroA aroD Arl A strain, PBCC222, was also tested in 38 volunteers. Formulation impacted on the determination of a safe and immunogenic dose; reconstituted lyophilized cultures required higher doses than the broth cultures to stimulate seroconversion. Ln general, doses which seroconverted the majority of group members produced undesirable symptoms regardless of attenuation or formulation. The inability to separate the presence of symptoms from achieving significant immunogenicity in these aroA aroD or aroA aroD htrA strains precludes their use as single dose typhoid vaccines in the formulations tested. Multiple doses of these strains at a lower, safe level may be effective as vectors for foreign antigens, (C) 2000 Elsevier Science Ltd. All rights reserved.