Correlation of T cell response and bacterial clearance in human volunteers challenged with Helicobacter pylori revealed by randomised controlled vaccination with Ty21a-based Salmonella vaccines.
Correlation of T cell response and bacterial clearance in human volunteers challenged with Helicobacter pylori revealed by randomised controlled vaccination with Ty21a-based Salmonella vaccines.
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DOI：
10.1136/gut.2007.145839
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发表时间：
2008-08
期刊：
影响因子：
24.5
通讯作者：
Meyer TF
中科院分区：
文献类型：
--
作者：
Aebischer T;Bumann D;Epple HJ;Metzger W;Schneider T;Cherepnev G;Walduck AK;Kunkel D;Moos V;Loddenkemper C;Jiadze I;Panasyuk M;Stolte M;Graham DY;Zeitz M;Meyer TF
幽门螺杆菌仍然是一个全球性的健康危害因素，而接种疫苗将是控制它的理想方法。自然感染似乎不会诱导保护性免疫。因此，人类疫苗的可行性存疑。
在两项前瞻性、随机、双盲、对照研究（保罗·埃尔利希研究所申请编号0802/02和1097/01）中，针对幽门螺杆菌的活疫苗在幽门螺杆菌血清学阴性且无活动性幽门螺杆菌感染证据的人类志愿者中进行了测试。志愿者（n = 58）口服接种表达幽门螺杆菌尿素酶或HP0231的伤寒沙门氏菌血清型Ty21a，或者仅接种Ty21a，然后用2×10⁵个cagPAI⁻幽门螺杆菌进行攻毒。对不良事件、感染情况、体液免疫、细胞免疫和黏膜免疫反应进行了监测。在接种疫苗前后以及攻毒后采集胃黏膜活检样本。感染用抗生素终止。
疫苗的耐受性良好。攻毒感染诱导了短暂的、轻度至中度的消化不良症状，以及慢性感染中已知的黏膜组织学和转录变化。疫苗未显示出令人满意的保护效果。然而，58名志愿者中有13名，其中8名接种疫苗者和5名对照者，呼气试验转为阴性，要么完全清除了幽门螺杆菌（5/13），要么减少了幽门螺杆菌负荷（8/13）。在这13名志愿者中的9名（69%）检测到幽门螺杆菌特异性辅助性T细胞，但在45名呼气试验阳性的志愿者中仅有6名（13%）检测到（p = 0.0002；费舍尔精确检验）。T细胞要么是由疫苗诱导产生的，要么是预先存在的，这取决于志愿者个体情况。
攻毒感染为疫苗测试提供了一个可控的模型。重要的是，它揭示了人类中针对幽门螺杆菌感染存在T细胞介导的免疫的证据。
Helicobacter pylori remains a global health hazard, and vaccination would be ideal for its control. Natural infection appears not to induce protective immunity. Thus, the feasibility of a vaccine for humans is doubtful. In two prospective, randomised, double-blind, controlled studies (Paul Ehrlich Institute application nos 0802/02 and 1097/01), live vaccines against H pylori were tested in human volunteers seronegative for, and without evidence of, active H pylori infection. Volunteers (n = 58) were immunised orally with Salmonella enterica serovar Typhi Ty21a expressing H pylori urease or HP0231, or solely with Ty21a, and then challenged with 2×105 cagPAI− H pylori. Adverse events, infection, humoral, cellular and mucosal immune response were monitored. Gastric biopsies were taken before and after vaccination, and postchallenge. Infection was terminated with antibiotics. Vaccines were well tolerated. Challenge infection induced transient, mild to moderate dyspeptic symptoms, and histological and transcriptional changes in the mucosa known from chronic infection. Vaccines did not show satisfactory protection. However, 13 of 58 volunteers, 8 vaccinees and 5 controls, became breath test negative and either cleared H pylori (5/13) completely or reduced the H pylori burden (8/13). H pylori-specific T helper cells were detected in 9 of these 13 (69%), but only in 6 of 45 (13%) breath test-positive volunteers (p = 0.0002; Fisher exact test). T cells were either vaccine induced or pre-existing, depending on the volunteer. Challenge infection offers a controlled model for vaccine testing. Importantly, it revealed evidence for T cell-mediated immunity against H pylori infection in humans.
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DOI：
10.1073/pnas.1635231100
发表时间：
2003-10-14
影响因子：
11.1
作者：
Mueller, A;O'Rourke, J;Falkow, S
通讯作者：
Falkow, S
影响因子：
3
作者：
Maecker, HT;Rinfret, A;Sekaly, RP
通讯作者：
Sekaly, RP
影响因子：
24.5
作者：
Graham, DY;Opekun, AR;Monath, TP
通讯作者：
Monath, TP
影响因子：
14.8
作者：
Chattopadhyay, Pratip K.;Yu, Joanne;Roederer, Mario
通讯作者：
Roederer, Mario
DOI：
10.1084/jem.188.12.2277
发表时间：
1998-12-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ermak TH;Giannasca PJ;Nichols R;Myers GA;Nedrud J;Weltzin R;Lee CK;Kleanthous H;Monath TP
通讯作者：
Monath TP