Development of a cost-effective protein-based combined glycoconjugate meningococcal-pneumococcal vaccine

这种细菌，脑膜炎奈瑟菌(Nm)和肺炎链球菌(Sp)，通常生活在人的喉咙后部。然而，它们也可以感染血液和大脑，导致一系列疾病，如肺炎和脑膜炎。脑膜炎是一种致命的疾病，可以在不到4小时内致死。脑膜炎的主要患者是四岁以下的儿童。有些疫苗是针对Nm和Sp的，已经使用多年，在限制疾病和预防死亡方面取得了一定程度的成功。然而，这些疫苗不能提供充分的保护，而且价格昂贵。因此，继续寻找新的、更便宜的Nm和Sp疫苗是明智的。在两项原则验证研究的第一项中，抗体(保护我们免受有害细菌侵袭的分子)在实验室中从脑膜炎康复者身上复制出来。从一名新城疫患者身上提取的抗体能够杀死多种新城疫类型；识别Sp的抗体的杀伤力目前正在评估中。这些杀手抗体识别的Nm和Sp蛋白可能是很好的候选疫苗。在第二项原理验证研究中，在实验室中使用被称为蛋白质-葡聚糖偶联技术(PGCT)的先进方法对一种著名的Nm疫苗成分进行了修改。这一PGCT将使生产更便宜和有效的疫苗成为可能。综上所述，这项研究的目的是：扩大这些有希望的初步研究，寻找更多杀死Nm和Sp菌株的抗体，特别是那些目前可用的疫苗没有覆盖的抗体。接下来，将明确确定抗体结合的Nm和Sp表面蛋白的身份--这些都是有希望的候选疫苗。随后，这些蛋白质(将优先考虑那些出现在尽可能多的Nm和Sp类型中的蛋白质)将被PGCT修饰。最后，将测试这些有希望的候选疫苗在动物身上诱导抗体产生的能力--这是在人类身上进行测试之前的必要步骤。这项研究的理想最终结果将是鉴定Nm和Sp蛋白，这些蛋白可以组成一种更便宜的预防脑膜炎的联合疫苗。

The bacteria, Neisseria meningitidis (Nm) and Streptococcus pneumoniae (Sp), normally live in the back of the throat of man. However, they can also infect the blood and the brain causing a range of diseases such as pneumonia and meningitis. Meningitis is a deadly disease that can kill in less than 4 hours. The main sufferers of meningitis are children under the age of four. Some vaccines exist against Nm and Sp and have been used for many years, with a degree of success in limiting disease and preventing death. However, these vaccines do not provide full protection and are expensive. Thus, it is sensible to continue the search for new, cheaper Nm and Sp vaccines. In the first of two proof-of-principle studies, antibodies (molecules that protect us from harmful germs) were reproduced in the laboratory from patients recovering from meningitis. Antibodies taken from a Nm patient were able to kill a broad selection of Nm types; the killing ability of antibodies recognising Sp are currently being assessed. The Nm and Sp proteins recognised by these killer antibodies may be good vaccine candidates. In the second proof-of-principle study, a well-known Nm vaccine component was modified in the lab using advanced methods known as protein-glycan coupling technology (PGCT). This PGCT will allow for the production of cheaper-to-produce and effective vaccines. From the foregoing, the aims of this study are: to extend these promising preliminary studies and find more antibodies that kill Nm and Sp strains, especially those that are not covered by currently-available vaccines. Next, the the identity of the proteins on the surface of Nm and Sp to which the antibodies bind will be unequivocally determined - these are promising vaccine candidates. Subsequently, these proteins (preference will be given to those that are present in as many Nm and Sp types as possible) will be modified with PGCT. Finally, the ability of these promising vaccine candidates to induce the production of antibodies in animals will be tested - a necessary step prior to testing in humans. The ideal end-result of this study will be the identification of Nm and Sp proteins that can compose a cheaper combined vaccine that will prevent meningitis.