Two studies evaluating the safety and immunogenicity of a live, attenuated Shigella flexneri 2a vaccine (SC602) and excretion of vaccine organisms in North American volunteers
Two studies evaluating the safety and immunogenicity of a live, attenuated Shigella flexneri 2a vaccine (SC602) and excretion of vaccine organisms in North American volunteers
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DOI：
10.1128/iai.72.2.923-930.2004
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发表时间：
2004-02-01
影响因子：
3.1
通讯作者：
Hale, TL
中科院分区：
文献类型：
--
作者：
Katz, DE;Coster, TS;Hale, TL
我们报告了对弗氏志贺氏菌 2a 菌株 SC602 的首次基于社区的评估，这是一种通过删除 icsA (virG) 质粒毒力基因而减毒的活口服疫苗菌株，给予 10(4) CFU。该试验的主要目的是确定疫苗的安全性和免疫原性，并确定定植的持续时间。 34 名志愿者中有 4 人出现短暂发烧，三人在研究的前 3 天报告腹泻。一半的志愿者对福氏链霉菌脂多糖产生了阳性血清免疫球蛋白 A (IgA) 反应。除一名志愿者外，所有志愿者都将疫苗通过粪便排出，持续 1 至 33 天，而且这种排泄通常是间歇性的。来自社区研究的数据得到了一项住院试验的补充，其中三名志愿者接受了 10(3) CFU，九名志愿者接受了 10(4) CFU。所有接受 10(3) CFU 的志愿者都会分泌 SC602，并产生 IgA 抗体分泌细胞反应。其中两个有血清 IgA 反应。接受 10(4) CFU 的 9 名志愿者中有 6 名排出了 SC602。一名疫苗接种者出现短暂发烧，两名疫苗接种者符合腹泻的定义。六名接受 10(4) CFU 的志愿者出现了抗体分泌细胞反应，四名志愿者出现了血清 IgA 反应。 SC602 现已在总共 58 名志愿者中以 10(4) CFU 进行了测试。这里和之前报道的这些临床试验的累积结果（Coster等人，Infect.Immun.67：3437-3443，1999）已经证明SC602是一种显着减毒的候选疫苗，可以在严格的人类疾病攻击模型中引起针对志贺菌病最严重症状的保护。
We report the first community-based evaluation of Shigella-flexneri 2a strain SC602, a live, oral vaccine strain attenuated by deletion of the icsA (virG) plasmid virulence gene, given at 10(4) CFU. The primary objectives of this trial were to determine the safety and immunogenicity of the vaccine and to determine the duration of colonization. Four of 34 volunteers experienced transient fevers, and three reported diarrhea during the first 3 days of the study. Half of the volunteers mounted a positive serum immunoglobulin A (IgA) response to S. flexneri lipopolysaccharide. All but one of the volunteers excreted the vaccine in their stools for 1 to 33 days, and this excretion was often intermittent. Data from the community-based study were supplemented with an inpatient trial in which three volunteers received 10(3) and nine received 10(4) CFU. All volunteers who received 10(3) CFU excreted SC602 and had an IgA antibody-secreting cell response. Two of these had a serum IgA response. Six of the nine volunteers who received 10(4) CFU excreted SC602. One vaccinee had a transient fever and two met the definition of diarrhea. Six volunteers that received 10(4) CFU had an antibody-secreting cell response, and four had a serum IgA response. SC602 has now been tested at 10(4) CFU in a total of 58 volunteers. The cumulative results of these clinical trials, reported here and previously (Coster et al., Infect. Immun. 67:3437-3443, 1999), have demonstrated that SC602 is a substantially attenuated candidate vaccine that can evoke protection against the most severe symptoms of shigellosis in a stringent human challenge model of disease.