Dissecting the host immune response to bacterial and HIV carbohydrate antigens to guide vaccine design

剖析宿主对细菌和 HIV 碳水化合物抗原的免疫反应以指导疫苗设计

• 批准号: MR/K024426/1
• 负责人: K Doores
• 金额: $ 135.07万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FK024426%2F1
• 关键词: Dissecting; host; immune; response; bacterial

Vaccines are important for preventing the spread of disease. Successful vaccines prepare the body's immune system to fight potentially deadly diseases by producing proteins called antibodies that identify and kill disease-causing agents like viruses and bacteria. Many infectious agents have carbohydrate structures on their surfaces. The bacterial vaccines used routinely to vaccinate infants work by producing antibodies that bind the specific carbohydrates on the bacterial surface. In addition, my previous work has also shown that a small number of HIV-infected patients produce antibodies that bind the carbohydrates on the virus surface and kill HIV. These observations suggest that vaccines designed to produce carbohydrate-binding antibodies could be successful at controlling disease spread. The aim of this project is to understand how the body makes these carbohydrate-specific antibodies during HIV infection and following vaccination with bacterial vaccines so that new vaccines can be made. This work will involve the isolation of carbohydrate-specific antibodies from HIV-infected patients and from individuals vaccinated with bacterial vaccines. I will determine what the antibodies look like and which carbohydrates the antibodies bind to. In the future we can use the information to design new carbohydrate-based vaccines that may prevent disease spread. Thus, in the long-term this research will have wide application to many infectious agents displaying carbohydrates on their surfaces and may potentially help prevent infectious diseases such as HIV.

疫苗对于预防疾病传播很重要。成功的疫苗通过产生称为抗体的蛋白质来识别和杀死病毒和细菌等致病因子，从而使身体的免疫系统做好准备，以对抗潜在的致命疾病。许多感染因子的表面都有碳水化合物结构。常规用于给婴儿接种疫苗的细菌疫苗通过产生与细菌表面的特定碳水化合物结合的抗体来发挥作用。另外，我之前的工作还表明，少数HIV感染者会产生抗体，与病毒表面的碳水化合物结合，杀死HIV。这些观察结果表明，旨在产生碳水化合物结合抗体的疫苗可以成功控制疾病传播。该项目的目的是了解人体在艾滋病毒感染期间以及接种细菌疫苗后如何产生这些碳水化合物特异性抗体，以便可以制造新疫苗。这项工作将涉及从艾滋病毒感染者和接种细菌疫苗的个体中分离碳水化合物特异性抗体。我将确定抗体的外观以及抗体与哪些碳水化合物结合。将来我们可以利用这些信息来设计新的碳水化合物疫苗，以防止疾病传播。因此，从长远来看，这项研究将广泛应用于许多表面具有碳水化合物的传染媒介，并可能有助于预防艾滋病毒等传染病。

项目成果

Determination of N-linked Glycosylation in Viral Glycoproteins by Negative Ion Mass Spectrometry and Ion Mobility.

• DOI: 10.1007/978-1-4939-2874-3_7
• 发表时间: 2015
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Bitto D;Harvey DJ;Halldorsson S;Doores KJ;Pritchard LK;Huiskonen JT;Bowden TA;Crispin M
• 通讯作者: Crispin M

The Tetrameric Plant Lectin BanLec Neutralizes HIV through Bidentate Binding to Specific Viral Glycans.

• DOI: 10.1016/j.str.2017.03.015
• 发表时间: 2017-05-02
• 期刊: Structure (London, England : 1993)
• 作者: Hopper JTS;Ambrose S;Grant OC;Krumm SA;Allison TM;Degiacomi MT;Tully MD;Pritchard LK;Ozorowski G;Ward AB;Crispin M;Doores KJ;Woods RJ;Benesch JLP;Robinson CV;Struwe WB
• 通讯作者: Struwe WB

HIV-1 Glycan Density Drives the Persistence of the Mannose Patch within an Infected Individual.

• DOI: 10.1128/jvi.01542-16
• 发表时间: 2016-12-15
• 期刊: Journal of virology
• 影响因子: 5.4
• 作者: Coss KP;Vasiljevic S;Pritchard LK;Krumm SA;Glaze M;Madzorera S;Moore PL;Crispin M;Doores KJ
• 通讯作者: Doores KJ

Targeting host-derived glycans on enveloped viruses for antibody-based vaccine design.

• DOI: 10.1016/j.coviro.2015.02.002
• 发表时间: 2015-04
• 期刊: Current opinion in virology
• 影响因子: 5.9
• 作者: Crispin M;Doores KJ
• 通讯作者: Doores KJ

Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein.

• DOI: 10.1016/j.celrep.2016.02.058
• 发表时间: 2016-03-22
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Behrens AJ;Vasiljevic S;Pritchard LK;Harvey DJ;Andev RS;Krumm SA;Struwe WB;Cupo A;Kumar A;Zitzmann N;Seabright GE;Kramer HB;Spencer DI;Royle L;Lee JH;Klasse PJ;Burton DR;Wilson IA;Ward AB;Sanders RW;Moore JP;Doores KJ;Crispin M
• 通讯作者: Crispin M