Characterisation of HiaNm, a novel outer membrane from Neisseria meningitidis; vaccine potential and functional studies

脑膜炎球菌性脑膜炎是一种毁灭性疾病，主要影响5岁以下儿童。临床表现是一种快速发展的疾病，发病率和死亡率高。这种疾病是由脑膜炎奈瑟菌（即脑膜炎球菌）引起的。目前有针对脑膜炎奈瑟菌血清A组和C组菌株的疫苗，但没有针对导致工业化国家大多数疾病的B组菌株的疫苗。我们最近发现了一个基因（命名为hiaNm），它编码一种新的蛋白质，这种蛋白质位于细菌表面的外膜上。在脑膜炎奈瑟菌外膜的所有成分的免疫学、生物化学和遗传学方面已经做了大量的工作。因此，这种新蛋白的发现为疫苗开发提供了一个令人兴奋的新方向。对于一种有效的疫苗，目标分子必须存在于大多数菌株中；我们已经证明hiaNm基因存在于所有被检测的菌株中。在本提案中，我们描述了hiaNm基因产物hiaNm的疫苗潜力和生物学功能的研究。我们将在高水平表达该蛋白，使小鼠免疫，并产生针对HiaNm的抗体，以发现它们是否能保护小鼠免受脑膜炎球菌病的侵害。在完成这组实验后，我们将处于有利地位，以评估进一步开发HiaNm作为脑膜炎球菌疫苗组成部分的潜力。

Meningococcal meningitis is a devastating illness which mostly affects children under 5 years. The clinical presentation is of a rapidly progressing disease with high rates of morbidity and mortality. This disease is caused by a bacterium, Neisseria meningitidis (the meningococcus). Vaccines are available against serogroup A and C strains of N. meningitidis, but not for group B strains, which cause the majority of disease in industrialised countries. We have recently identified a gene (designated hiaNm) which encodes a new protein which is located on the surface of the bacterium, in the outer membrane. There has been an enormous body of work done on the immunology, biochemistry and genetics of all components of the outer membrane of Neisseria meningitidis. Therefore the discovery of this novel protein provides an exciting opportunity to take a new direction in vaccine development. For an effective vaccine, the target molecule must be present in most strains; we have already shown that the hiaNm gene is present in all strains examined. In this proposal we describe a study of the vaccine potential and biological function of the hiaNm gene product HiaNm. We will express the protein at high levels, immunise mice, and produce antibodies against HiaNm to discover whether they can protect mice against meningococcal disease. At the completion of this set of experiments we will be in an excellent position to assess the potential for the further development of HiaNm as a component of a meningococcal vaccine.