Investigations into the mechanism of vaccine- induced protection against the gastric pathogen Helicobacter pylori.

幽门螺杆菌是世界上最常见的胃肠道病原体，感染澳大利亚人口的比例高达20%。感染被认为是在儿童时期获得的，可能会导致急性或慢性胃炎，以及以后的生活中的胃溃疡。幽门螺杆菌感染也与胃癌的发生密切相关，胃癌是全球第二大癌症死亡原因。从长远来看，疫苗将是控制这种疾病的最好和最具成本效益的方法。在实验动物模型中接种幽门螺杆菌疫苗是有效的。一些疫苗已经进入了在人类志愿者身上进行临床试验的早期阶段，但结果令人失望。我们仍然不知道接种疫苗是如何导致杀死胃里的细菌的，尽管我们知道抗体不是原因。更好地了解疫苗在老鼠体内的工作原理将有助于为人类设计疫苗。在一种研究疫苗接种的新方法中，利用DNA微阵列技术分析了免疫小鼠胃中的基因表达模式。通过这种方式，我们确定了几个新的基因，结果我们发展了一种新的理论，即疫苗接种如何导致杀死幽门螺杆菌。我们认为，控制胃中幽门螺杆菌的因素是多种因素共同作用的结果：瘦素，主要被称为肥胖基因，是一种由脂肪细胞产生的激素，控制食欲。最近，瘦素也被证明可以影响胃粘膜中的免疫细胞(T细胞)。这些T细胞继而向胃表面的(上皮)细胞发送信号，诱导它们产生其他蛋白质；我们认为其中一些蛋白质可能会减缓快速游泳的幽门螺杆菌细菌的速度，以及一些小的抗微生物蛋白质(防御素)，这些蛋白质能够通过在细菌的膜上打洞来直接杀死细菌。这项研究的结果将被用来帮助设计更好的人类幽门螺杆菌疫苗。

Helicobacter pylori (H. pylori) is the most common gastro-intestinal pathogen worldwide and infects up to 20 % of the Australian population. Infection is thought to be acquired in childhood, and may cause acute or chronic gastritis, and gastric ulcer later in life. H. pylori infection is also strongly associated with the development of gastric cancer, the second most common cause of cancer death world- wide. In the long term a vaccine will be the best and most cost effective way to control this disease. Vaccination against H. pylori is effective in laboratory animal models. A few vaccines have entered the early phases of clinical trials in human volunteers, however the results have been disappointing. We still do not understand how vaccination leads to killing of bacteria in the stomach, although it is known that antibodies are not responsible. A better understanding of how vaccination works in mice will help the design of vaccines for humans. In a novel approach to study vaccination, the gene expression pattern in the stomachs of immunized mice was analyzed using DNA micro-array technology. In this way we identified several novel genes, and as a result we have developed a new theory for how vaccination might lead to killing H. pylori. We propose that a combination of factors, act together to control H. pylori in the stomach: Leptin, known chiefly as the Obese gene, is a hormone produced by fat cells and controls appetite. Recently leptin has also been shown to influence immune cells (T- cells) in the stomach mucosa. These T-cells in turn send signals to the (epithelial) cells on the surface of the stomach which induces them to produce other proteins; some of which we believe may slow the fast-swimming H. pylori bacteria, and some small anti-microbial proteins (defensins), which are able to kill the bacteria directly by making holes in their membranes. The results of this research will be used to help design better H. pylori vaccines for humans.