PDF(Pubmed)
Abstract：
Invasive non-typhoidal Salmonellosis (iNTS) is mainly caused by Salmonella enterica serovars Typhimurium and Enteritidis and is estimated to result in 77 500 deaths per year, disproportionately affecting children under 5 years of age in sub-Saharan Africa. Invasive non-typhoidal Salmonellae serovars are increasingly acquiring resistance to first-line antibiotics, thus an effective vaccine would be a valuable tool in reducing morbidity and mortality from infection. While NTS livestock vaccines are in wide use, no licensed vaccines exist for use in humans. Here, a first-in-human study of a novel vaccine (iNTS-GMMA) containing S. Typhimurium and S. Enteritidis Generalised Modules for Membrane Antigens (GMMA) outer membrane vesicles is presented.
The Salmonella Vaccine Study in Oxford is a randomised placebo-controlled participant-observer blind phase I study of the iNTS-GMMA vaccine. Healthy adult volunteers will be randomised to receive three intramuscular injections of the iNTS-GMMA vaccine, containing equal quantities of S. Typhimurium and S. Enteritidis GMMA particles adsorbed on Alhydrogel, or an Alhydrogel placebo at 0, 2 and 6 months. Participants will be sequentially enrolled into three groups: group 1, 1:1 randomisation to low dose iNTS-GMMA vaccine or placebo; group 2, 1:1 randomisation to full dose iNTS-GMMA vaccine or placebo; group 3, 2:1 randomisation to full dose or lower dose (dependant on DSMC reviews of groups 1 and 2) iNTS-GMMA vaccine or placebo.The primary objective is safety and tolerability of the vaccine. The secondary objective is immunogenicity as measured by O-antigen based ELISA. Further exploratory objectives will characterise the expanded human immune profile.
Ethical approval for this study has been obtained from the South Central-Oxford A Research Ethics Committee (Ethics REF:22/SC/0059). Appropriate documentation and regulatory approvals have been acquired. Results will be disseminated via peer-reviewed articles and conferences.
EudraCT Number: 2020-000510-14.
The Salmonella Vaccine Study in Oxford is a randomised placebo-controlled participant-observer blind phase I study of the iNTS-GMMA vaccine. Healthy adult volunteers will be randomised to receive three intramuscular injections of the iNTS-GMMA vaccine, containing equal quantities of S. Typhimurium and S. Enteritidis GMMA particles adsorbed on Alhydrogel, or an Alhydrogel placebo at 0, 2 and 6 months. Participants will be sequentially enrolled into three groups: group 1, 1:1 randomisation to low dose iNTS-GMMA vaccine or placebo; group 2, 1:1 randomisation to full dose iNTS-GMMA vaccine or placebo; group 3, 2:1 randomisation to full dose or lower dose (dependant on DSMC reviews of groups 1 and 2) iNTS-GMMA vaccine or placebo.The primary objective is safety and tolerability of the vaccine. The secondary objective is immunogenicity as measured by O-antigen based ELISA. Further exploratory objectives will characterise the expanded human immune profile.
Ethical approval for this study has been obtained from the South Central-Oxford A Research Ethics Committee (Ethics REF:22/SC/0059). Appropriate documentation and regulatory approvals have been acquired. Results will be disseminated via peer-reviewed articles and conferences.
EudraCT Number: 2020-000510-14.
摘要：
背景：侵袭性非伤寒沙门氏菌病（iNTS）主要由鼠伤寒沙门氏菌和肠炎沙门氏菌引起，估计每年导致77,500人死亡，对撒哈拉以南非洲5岁以下儿童的影响不成比例。侵袭性非伤寒沙门氏菌血清变型越来越多地获得对一线抗生素的耐药性，因此，有效的疫苗将是降低感染发病率和死亡率的有价值的工具。虽然NTS家畜疫苗被广泛使用，不存在用于人类的许可疫苗。这里,介绍了一种新型疫苗（iNTS-GMMA）的首次人体研究，该疫苗包含鼠伤寒沙门氏菌和肠炎沙门氏菌膜抗原（GMMA）外膜囊泡的通用模块。
方法：牛津的沙门氏菌疫苗研究是一项关于iNTS-GMMA疫苗的随机安慰剂对照参与者-观察者盲I期研究。健康的成年志愿者将随机接受三次肌内注射iNTS-GMMA疫苗，含有等量的吸附在Alhydrogel上的鼠伤寒沙门氏菌和肠炎沙门氏菌GMMA颗粒，或在0、2和6个月服用Alhydrogel安慰剂。参与者将依次分为三组：第1组，1：1随机分配给低剂量iNTS-GMMA疫苗或安慰剂；第2组，1：1随机分配给全剂量iNTS-GMMA疫苗或安慰剂；第3组，2：1随机分配给全剂量或低剂量（取决于第1组和第2组的DSMC评论）iNTS-GMMA疫苗或安慰剂。主要目标是疫苗的安全性和耐受性。第二个目的是通过基于O-抗原的ELISA测量的免疫原性。进一步的探索目标将表征扩大的人类免疫谱。
背景：这项研究的伦理批准已从牛津中南部A研究伦理委员会获得（伦理学REF：22/SC/0059）。已获得适当的文件和监管批准。结果将通过同行评审的文章和会议传播。
背景：EudraCT编号：2020-000510-14。
方法：牛津的沙门氏菌疫苗研究是一项关于iNTS-GMMA疫苗的随机安慰剂对照参与者-观察者盲I期研究。健康的成年志愿者将随机接受三次肌内注射iNTS-GMMA疫苗，含有等量的吸附在Alhydrogel上的鼠伤寒沙门氏菌和肠炎沙门氏菌GMMA颗粒，或在0、2和6个月服用Alhydrogel安慰剂。参与者将依次分为三组：第1组，1：1随机分配给低剂量iNTS-GMMA疫苗或安慰剂；第2组，1：1随机分配给全剂量iNTS-GMMA疫苗或安慰剂；第3组，2：1随机分配给全剂量或低剂量（取决于第1组和第2组的DSMC评论）iNTS-GMMA疫苗或安慰剂。主要目标是疫苗的安全性和耐受性。第二个目的是通过基于O-抗原的ELISA测量的免疫原性。进一步的探索目标将表征扩大的人类免疫谱。
背景：这项研究的伦理批准已从牛津中南部A研究伦理委员会获得（伦理学REF：22/SC/0059）。已获得适当的文件和监管批准。结果将通过同行评审的文章和会议传播。
背景：EudraCT编号：2020-000510-14。
