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

脑膜炎奈瑟菌（Nm）和肺炎链球菌（Sp）这两种细菌通常生活在人的喉咙后部。然而，它们也会感染血液和大脑，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，可在4小时内致人死亡。脑膜炎的主要患者是四岁以下的儿童。一些针对Nm和Sp的疫苗已经使用多年，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、更便宜的纳米和Sp疫苗是明智的。在两项原理验证研究中的第一项中，抗体（保护我们免受有害细菌侵害的分子）在实验室中从脑膜炎恢复期的患者身上复制出来。从Nm患者身上提取的抗体能够杀死多种Nm类型；目前正在评估识别Sp的抗体的杀伤能力。这些杀伤抗体识别的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，利用先进的蛋白质-聚糖偶联技术（PGCT）在实验室对一种著名的纳米疫苗成分进行了修饰。这种PGCT将允许生产生产成本更低和有效的疫苗。综上所述，本研究的目的是：扩展这些有希望的初步研究，发现更多杀死Nm和Sp菌株的抗体，特别是那些目前可用疫苗未覆盖的抗体。接下来，抗体结合的Nm和Sp表面蛋白质的身份将被明确确定-这些是有希望的疫苗候选物。随后，这些蛋白（将优先考虑那些存在于尽可能多的Nm和Sp型中的蛋白）将被PGCT修饰。最后，将测试这些有希望的候选疫苗在动物体内诱导产生抗体的能力——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出Nm和Sp蛋白，它们可以组成一种更便宜的联合疫苗，预防脑膜炎。

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.