VACCINE DEVELOPMENT IN TUBERCULOSIS

结核病疫苗的开发

• 批准号: 6849736
• 负责人: Antonio Campos-Neto
• 金额: $ 33.38万
• 依托单位: ADA FORSYTH INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6849736
• 关键词: Macaca fascicularis; Mycobacterium tuberculosis; T lymphocyte; active immunization; bacterial antigens; cellular immunity; clinical research; guinea pigs; human subject; laboratory mouse; leukocyte activation /transformation; molecular cloning; recombinant proteins; tuberculosis vaccines; vaccine development; vector vaccine

This proposal is designed to identify, characterize, and clone Mycobacterium tuberculosis genes encoding proteins associated with specific T cell responses of presumed protected humans and animals. Antigens associated with both CD4+ and/or CD8+ T cell responses are the target of this proposal. The recent identification, by our group, of a novel and protective antigen opens new possibilities for vaccine development. Two other antigens/gene have been cloned, expressed, and purified. They will be evaluated for their ability to elicit T cell responses from human PBMC, primarily from non-BCG immunized PPD+ healthy individuals. The recombinant antigens alone and in combination will also be evaluated as vaccine candidates in three animal protection models, including mice, guinea pigs, and cynomolgus monkeys, all of which will be challenged by aerosol or intratracheal routes. In addition to the evaluation of these antigens, we will characterize and clone other vaccine candidates using recently developed approaches for the direct identification of both CD4 and CD8 T cell antigens.

该提案旨在鉴定、表征和克隆结核分枝杆菌基因，该基因编码与假定受保护的人类和动物的特异性T细胞应答相关的蛋白质。 与CD 4+和/或CD 8 + T细胞应答相关的抗原是该提议的目标。 我们小组最近鉴定出一种新的保护性抗原，为疫苗开发开辟了新的可能性。 另外两种抗原/基因已被克隆、表达和纯化。 将评价它们从人PBMC（主要来自非BCG免疫的PPD+健康个体）中引发T细胞应答的能力。还将在三种动物保护模型（包括小鼠、豚鼠和食蟹猴）中评价重组抗原单独和组合作为候选疫苗，所有动物均将通过气雾剂或肠道途径进行攻毒。除了这些抗原的评价，我们将表征和克隆其他候选疫苗使用最近开发的方法直接识别CD 4和CD 8 T细胞抗原。

项目成果

Potential serological use of a recombinant protein that is a replica of a Mycobacterium tuberculosis protein found in the urine of infected mice.

重组蛋白的潜在血清学用途，该蛋白是受感染小鼠尿液中发现的结核分枝杆菌蛋白的复制品。

• DOI: 10.1128/cdli.11.2.280-286.2004
• 发表时间: 2004
• 期刊: Clinical and diagnostic laboratory immunology
• 作者: Mukherjee,Sandeep;Daifalla,Nada;Zhang,Yanni;Douglass,John;Brooks,Lisa;Vedvick,Thomas;Houghton,Raymond;Reed,StevenG;Campos-Neto,Antonio
• 通讯作者: Campos-Neto,Antonio

Expression and purification of immunologically reactive DPPD, a recombinant Mycobacterium tuberculosis skin test antigen, using Mycobacterium smegmatis and Escherichia coli host cells.

使用耻垢分枝杆菌和大肠杆菌宿主细胞表达和纯化免疫反应性 DPPD（一种重组结核分枝杆菌皮试抗原）。

• DOI: 10.1139/w03-109
• 发表时间: 2004
• 期刊: Canadian journal of microbiology.
• 作者: Liu,Chao;Flamoe,Eric;Chen,Hong-Jing;Carter,Darrick;Reed,StevenG;Campos-Neto,Antonio
• 通讯作者: Campos-Neto,Antonio

Alternative approach to express Mycobacterium tuberculosis proteins in Escherichia coli.

在大肠杆菌中表达结核分枝杆菌蛋白的替代方法。

• DOI: 10.2144/03351bm02
• 发表时间: 2003
• 期刊: BioTechniques
• 影响因子: 2.7
• 作者: Mukherjee,Sandeep;Daifalla,Nada;Liu,Chao;Campos-Neto,Antonio
• 通讯作者: Campos-Neto,Antonio

Skin test performed with highly purified Mycobacterium tuberculosis recombinant protein triggers tuberculin shock in infected guinea pigs.

使用高度纯化的结核分枝杆菌重组蛋白进行的皮肤测试会在受感染的豚鼠中引发结核菌素休克。

• DOI: 10.1128/iai.73.6.3301-3306.2005
• 发表时间: 2005
• 期刊: Infection and immunity.
• 作者: Reece,StephenT;Stride,Nicole;Ovendale,Pamela;Reed,StevenG;Campos-Neto,Antonio
• 通讯作者: Campos-Neto,Antonio