International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh.
Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
Helicobacter. 2019 Dec;24(6):e12658. doi: 10.1111/hel.12658. Epub 2019 Sep 9.
Chronic Helicobacter pylori infection is the cause of peptic ulcers in a subpopulation of individuals and a risk factor for the development of gastric cancer. A vaccine against H pylori infection can prevent the acquisition of the infection and protect against reinfections. Clinical trials to date evaluating the efficacy of H pylori vaccines in human challenge models have shown moderate to poor protection with difficulties in predicting efficacy. Thus, while further studies are needed to design an effective vaccine, we also need to find relevant correlates for vaccine efficacy.
To find immune correlates to vaccine efficacy, the frequencies of neutrophils, eosinophils and inflammatory monocytes and CD4 T-cell memory and mucosa homing integrin α4β7 cells were assessed by flow cytometry in the blood of mice after vaccination.
H pylori antigens and cholera toxin or the multiple mutant CT (mmCT) were administered via the sublingual (SL) and intragastric route (IG). The vaccinated mice were infected with H pylori strain SS1 bacteria, and colonization in the stomach and immune responses were evaluated.
The H pylori vaccine was effective in reducing bacterial load in the stomach of mice and enhancing immune responses compared to unvaccinated infection controls. In the blood of mice after SL or IG route of vaccination, we observed changes in frequencies of innate and adaptive immune cell subsets compared to infection controls. Remarkably, the frequency of circulating mucosal homing α4β7 CD4 T cells after vaccination correlated with low bacterial load in the stomach of individual mice irrespective of the immunization route.
Our study shows that the innate and adaptive immune cell subsets can be measured in the blood after vaccination and that increased frequency of α4β7 CD4 in the blood after immunization could be used as a predictive marker for the efficacy of vaccine against H pylori infection.
慢性幽门螺杆菌感染是部分人群发生消化性溃疡的病因，也是胃癌发生的危险因素。针对幽门螺杆菌的疫苗可以预防感染的获得并防止再感染。迄今为止，在人类挑战模型中评估幽门螺杆菌疫苗疗效的临床试验显示出中等至较差的保护作用，并且难以预测疗效。因此，虽然需要进一步的研究来设计有效的疫苗，但我们也需要找到与疫苗疗效相关的指标。
为了寻找与疫苗疗效相关的免疫指标，通过流式细胞术评估了疫苗接种后小鼠血液中中性粒细胞、嗜酸性粒细胞和炎症性单核细胞以及 CD4 记忆 T 细胞和黏膜归巢整合素 α4β7 细胞的频率。
通过舌下（SL）和胃内（IG）途径给予幽门螺杆菌抗原和霍乱毒素或多重突变 CT（mmCT）。接种疫苗的小鼠感染幽门螺杆菌 SS1 菌株，评估胃部定植和免疫反应。
与未接种感染对照相比，幽门螺杆菌疫苗可有效降低小鼠胃部的细菌负荷并增强免疫反应。与感染对照相比，在 SL 或 IG 途径接种疫苗后，我们观察到小鼠血液中固有和适应性免疫细胞亚群的频率发生了变化。值得注意的是，接种疫苗后循环黏膜归巢 α4β7 CD4 T 细胞的频率与个体小鼠胃部的低细菌负荷相关，而与免疫途径无关。
我们的研究表明，在接种疫苗后可以在血液中测量到固有和适应性免疫细胞亚群，并且免疫后 α4β7 CD4 细胞的频率增加可以作为预测幽门螺杆菌感染疫苗疗效的指标。
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