Department of Microbiology and Immunology, University of Gothenburg Vaccine Research Institute, Gothenburg, Sweden.
Vaccine. 2011 Feb 1;29(6):1235-41. doi: 10.1016/j.vaccine.2010.11.088. Epub 2010 Dec 13.
HpaA is a Helicobacter pylori-specific lipoprotein that has been shown to be an effective protective antigen for mucosal vaccination against H. pylori infection in mice. However, detergents are needed for the purification of full-length HpaA (HpaA(full)), which might confer toxicity, thus making HpaA(full) unsuitable for use in a human vaccine. We here describe a recombinantly produced truncated version of HpaA (HpaA(trunc)), which is easily purified without the use of detergents. Evaluation in the murine H. pylori infection model showed that sublingual immunization with HpaA(trunc) was equally immunogenic and protective as immunization with HpaA(full). Immunization with a combination of HpaA(trunc) and recombinant UreB protein induced strong immune responses to both antigens and importantly had a strong synergistic effect on protection, associated with synergistically increased expression of IL-17 in the stomach. Notably, sublingual immunization with HpaA(trunc) and UreB was superior to corresponding intragastric immunization with regard to the level of protection induced. In conclusion, HpaA(trunc) is a promising, readily produced, non-toxic recombinant antigen for inclusion in a mucosal vaccine against H. pylori infection, which may preferably be given sublingually together with UreB.
HpaA 是一种幽门螺杆菌特异性脂蛋白，已被证明是针对幽门螺杆菌感染的黏膜疫苗接种的有效保护性抗原，在小鼠中。然而，全长 HpaA（HpaA(full)）的纯化需要去污剂，这可能会导致毒性，因此不适合用于人类疫苗。我们在此描述了一种重组产生的 HpaA 截断版本（HpaA(trunc)），它无需使用去污剂即可轻松纯化。在小鼠幽门螺杆菌感染模型中的评估表明，HpaA(trunc)的舌下免疫与 HpaA(full)的免疫同样具有免疫原性和保护作用。用 HpaA(trunc)和重组 UreB 蛋白的组合免疫诱导了对两种抗原的强烈免疫反应，并且重要的是对保护具有强烈的协同作用，与胃中 IL-17 的协同增加表达相关。值得注意的是，与相应的胃内免疫相比，HpaA(trunc)和 UreB 的舌下免疫在诱导的保护水平方面更具优势。总之，HpaA(trunc)是一种有前途的、易于生产的、无毒的重组抗原，可用于包含在针对幽门螺杆菌感染的黏膜疫苗中，最好与 UreB 一起舌下给予。
