MUCOSAL VACCINES AGAINST GONORRHEA
淋病粘膜疫苗
基本信息
- 批准号:6374378
- 负责人:
- 金额:$ 32.11万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2000
- 资助国家:美国
- 起止时间:2000-06-01 至 2004-05-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION: (Adapted from Applicant's Abstract) The objective of this proposal
is to evaluate the use of a newly discovered, highly conserved outer-membrane
protein antigen of Neisseria gonorrhoeae, designated NspA, as a potential
candidate vaccine against gonorrhea, when administered by mucosal routes
designed to induce high levels of antibodies in the genital tract. This will be
accomplished by exploiting a novel technology, developed in this laboratory,
for fusing bacterial protein antigens to the A2 subunit of cholera toxin (CT)
and co-expressing the fusion protein with the nontoxic binding (B) subunit of
CT, to form chimeric immunogens of the form NspA-CTA2/B, in which the toxic A1
subunit of CT has been replaced by the desired antigen. Chemical conjugates of
NspA and CTB will also be evaluated. Alternative constructs will utilize type
II heat-labile enterotoxins of Escherichia coli, which have different binding
properties. Immunogens of this type have previously been shown to induce strong
mucosa and circulating antibody responses when administered by mucosal routes.
Specific IgA and IgG antibody responses in the genital tract (and other mucosal
sites) and in the serum will be determined in mice immunized with these
constructs as applied by intranasal or intragastric routes. Specific antibody
secreting cells, specific T cells and the cytokines secreted by T cells will
also be evaluated to assess the immune response in detail. A newly described
mouse model of genital tract colonization by N. gonorrhoeae will be used to
determine the ability of NspA-CTA2/B chimeric proteins and other constructs to
elicit protective immunity against gonococcal infection. Potential mechanisms
by which the expected IgA and IgG antibodies to NspA may be effective in
protection against gonococcal infection of the genital tract will be examined
by developing monoclonal IgA and IgG antibodies from mice mucosally immunized
with NspA-CTA2/B constructs, and testing their ability to inhibit gonococcal
adherence to and invasion of epithelial cells in culture, and to suppress
genital colonization of mice with N. gonorrhoeae. The successful accomplishment
of these objectives should provide a basis for further considering NspA as a
component of a vaccine against gonorrhea, and for proposing trials designed to
evaluate human genital tract immune responses to NspA-CTA2/B chimeric proteins.
The information gained about genital tract immunity and the techniques used may
also be applicable to other sexually transmitted diseases.
描述:(改编自申请人摘要)本提案的目的
是评估一种新发现的高度保守的外膜的使用,
淋病奈瑟菌的蛋白抗原,命名为NspA,作为一种潜在的
经粘膜途径接种的淋病候选疫苗
设计用来在生殖道中诱导高水平的抗体。这将是
通过利用这个实验室开发的一种新技术,
用于将细菌蛋白抗原与霍乱毒素(CT)的A2亚单位融合
以及共表达所述融合蛋白与以下的无毒结合(B)亚基:
CT,以形成形式NspA-CTA 2/B的嵌合免疫原,其中毒性A1
CT亚基已被所需抗原取代。的化学共轭物
还将对NspA和CTB进行评价。替代构造将利用类型
II大肠杆菌不耐热肠毒素,其具有不同的结合
特性.这种类型的免疫原先前已显示出诱导强烈的
当通过粘膜途径施用时,粘膜和循环抗体应答。
生殖道(和其他粘膜)中的特异性伊加和IgG抗体应答
将在用这些免疫的小鼠中测定
如通过鼻内或胃内途径施用的构建体。特异性抗体
分泌细胞、特异性T细胞和T细胞分泌的细胞因子将
还可以进行评估,以详细评估免疫反应。一种新描述的
小鼠生殖道定植模型。淋病将用于
确定NspA-CTA 2/B嵌合蛋白和其它构建体
引发针对淋球菌感染的保护性免疫。潜在机制
预期的针对NspA的伊加和IgG抗体可以有效地
将研究防止生殖道淋球菌感染的措施。
通过从粘膜免疫的小鼠中开发单克隆伊加和IgG抗体,
与NspA-CTA 2/B构建体,并测试它们抑制淋球菌感染的能力,
粘附和侵袭培养的上皮细胞,并抑制
小鼠生殖器定植N.淋病成功完成
这些目标应提供进一步考虑NspA作为一个基础,
淋病疫苗的组成部分,并提出旨在
评价人生殖道对NspA-CTA 2/B嵌合蛋白的免疫应答。
获得的关于生殖道免疫和所用技术的信息可能
也适用于其他性传播疾病。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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MICHAEL W RUSSELL其他文献
MICHAEL W RUSSELL的其他文献
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{{ truncateString('MICHAEL W RUSSELL', 18)}}的其他基金
Imaging antigen and adjuvant uptake for enhancing response to mucosal vaccines
对抗原和佐剂摄取进行成像以增强对粘膜疫苗的反应
- 批准号:
8204418 - 财政年份:2010
- 资助金额:
$ 32.11万 - 项目类别:
Imaging antigen and adjuvant uptake for enhancing response to mucosal vaccines
对抗原和佐剂摄取进行成像以增强对粘膜疫苗的反应
- 批准号:
8029985 - 财政年份:2010
- 资助金额:
$ 32.11万 - 项目类别:
MATERNAL INFLUENCES ON MUCOSAL IMMUNITY IN INFANTS
母亲对婴儿粘膜免疫的影响
- 批准号:
6104901 - 财政年份:1998
- 资助金额:
$ 32.11万 - 项目类别:
MATERNAL INFLUENCES ON MUCOSAL IMMUNITY IN INFANTS
母亲对婴儿粘膜免疫的影响
- 批准号:
6238572 - 财政年份:1997
- 资助金额:
$ 32.11万 - 项目类别:
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