A novel vaccine for broad protection against meningococcal disease: progression to phase I clinical trial

一种可广泛预防脑膜炎球菌病的新型疫苗：进展至 I 期临床试验

• 批准号: MR/M007693/1
• 负责人: Andrew Pollard
• 金额: $ 174.78万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FM007693%2F1
• 关键词: novel; vaccine; broad; protection; against

The aim of this project is to progress a novel vaccine against serogroup B meningococcal disease (MenB) to phase I clinical trial. MenB disease is the leading infectious cause of death in children in the UK. Two vaccine candidates are under development or recently licensed, based on recombinant proteins and outer membrane vesicles. The recently licensed vaccine was not considered to be cost-effective for infant immunisation in one recent analysis, as it requires up to 4 injections, and the other one is being developed for use in adolescents only. Therefore both have serious limitations if protection is to be provided for the population at most risk: infants under one year of age. Ongoing development of alternative or improved vaccine candidates is therefore required to reduce the cost of vaccine production and delivery. Our proposed solution is to use a novel vaccine platform to deliver a major meningococcal antigen-target to the immune system. This approach is new as the delivery platform has never been used before for inducing antibody responses against bacterial outer membrane proteins. The rational is that the novel vaccine delivery system induces both innate and adaptive immune responses in mammalian hosts, including robust IFN-gamma responses, thought to provide the ideal conditions for switching B cells to produce complement-fixing bactericidal antibody, unlike conventional unadjuvanted or aluminium-based adjuvanted vaccines. We have already demonstrated in pre-clinical models that a single dose of this vaccine candidate induces strong and rapid functional antibody responses including high serum bactericidal antibody titres. The next step of the development plan is thus to progress this promising vaccine candidate into a phase I clinical trial.

本项目的目的是将一种新的抗血清群B脑膜炎球菌病（MenB）的疫苗进展到I期临床试验。MenB疾病是英国儿童死亡的主要传染性原因。基于重组蛋白和外膜囊泡的两种候选疫苗正在开发中或最近获得许可。在最近的一项分析中，最近获得许可的疫苗被认为对婴儿免疫不具有成本效益，因为它需要多达4次注射，另一种疫苗正在开发中，仅用于青少年。因此，如果要为最危险的人口-一岁以下的婴儿-提供保护，这两项法律都有严重的局限性。因此，需要不断开发替代或改进的候选疫苗，以降低疫苗生产和交付的成本。我们提出的解决方案是使用一种新的疫苗平台，将主要的脑膜炎球菌抗原靶向免疫系统。这种方法是新的，因为递送平台以前从未用于诱导针对细菌外膜蛋白的抗体应答。其理由是，新的疫苗递送系统在哺乳动物宿主中诱导先天性和适应性免疫应答，包括稳健的IFN-γ应答，被认为提供了转换B细胞以产生补体固定杀菌抗体的理想条件，这与常规的无佐剂或基于铝的佐剂疫苗不同。我们已经在临床前模型中证明，单剂量的这种候选疫苗诱导强烈和快速的功能性抗体应答，包括高血清杀菌抗体滴度。因此，开发计划的下一步是将这种有希望的候选疫苗进展到I期临床试验。

项目成果

Viral vectors expressing group B meningococcal outer membrane proteins induce strong antibody responses but fail to induce functional bactericidal activity.

表达B组脑膜炎球菌外膜蛋白的病毒载体诱导强烈的抗体反应，但不能诱导功能性杀菌活性。

• DOI: 10.1016/j.jinf.2022.02.032
• 发表时间: 2022
• 期刊: The Journal of infection
• 作者: Marsay L

Application of a Neisseria meningitidis antigen microarray to identify candidate vaccine proteins from a human Phase I clinical trial

• DOI: 10.1016/j.vaccine.2022.05.032
• 发表时间: 2022-06-10
• 期刊: VACCINE
• 影响因子: 5.5
• 作者: Chang, Chun-Mien;Awanye, Amaka M.;Derrick, Jeremy P.
• 通讯作者: Derrick, Jeremy P.

MAIT cell activation augments adenovirus vector vaccine immunogenicity.

• DOI: 10.1126/science.aax8819
• 发表时间: 2021-01-29
• 期刊: Science (New York, N.Y.)
• 作者: Provine NM;Amini A;Garner LC;Spencer AJ;Dold C;Hutchings C;Silva Reyes L;FitzPatrick MEB;Chinnakannan S;Oguti B;Raymond M;Ulaszewska M;Troise F;Sharpe H;Morgan SB;Hinks TSC;Lambe T;Capone S;Folgori A;Barnes E;Rollier CS;Pollard AJ;Klenerman P
• 通讯作者: Klenerman P

Gene expression profiling reveals insights into infant immunological and febrile responses to group B meningococcal vaccine.

• DOI: 10.15252/msb.20209888
• 发表时间: 2020-11
• 期刊: Molecular systems biology
• 影响因子: 9.9
• 作者: O'Connor D;Pinto MV;Sheerin D;Tomic A;Drury RE;Channon-Wells S;Galal U;Dold C;Robinson H;Kerridge S;Plested E;Hughes H;Stockdale L;Sadarangani M;Snape MD;Rollier CS;Levin M;Pollard AJ
• 通讯作者: Pollard AJ