Monoclonal Antibodies for the Study of P. carinii

用于卡氏疟原虫研究的单克隆抗体

基本信息

批准号：
7878315
负责人：
Francis Gigliotti
金额：
$ 0.66万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-14 至 2009-10-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): This ongoing research project has had as its long-term goal utilizing the technology of monoclonal antibody (mab) production as a tool to better understand P. carinii host-parasite interactions. We are particularly interested in utilizing passive and active immunotherapy to prevent or treat P. carinii pneumonia (Pcp). During the last grant period we showed that one of the mab that we produced conferred significant protection against Pcp. Furthermore, we have been able to use that mab to identify the "protective" epitope recognized by the antibody as well as identifying two P. carinii antigens (A12 and KEX1) which contain this epitope of interest. Based on our progress to date, we propose two overriding goals for this project. Our first goal is to characterize and exploit this protective antigen-antibody interaction for the purpose of developing active and passive immunization for the prevention of Pcp. Our second goal is to define the effect of passive immunotherapy, with specific antibody, on the outcome of active Pcp with particular emphasis on the effect of antibody on the immunopathogenesis of lung injury during Pcp. To achieve these two goals we propose the following specific aims: 1) We will clone and characterize the complete cDNA of the gene encoding the A12 polypeptide and determine whether the A12 antigen is localized to the surface of P. carinii. 2) We will define the immunogenicity and efficacy of active immunization with recombinant antigens containing the epitopes recognized by mab 4F11. 3) We will examine the effect of passive antibody administration on established Pcp. Specifically, we will define the effect of passive antibody therapy on immune-mediated lung injury observed during Pcp. We will also determine the microbiologic effect of combining passive antibody therapy with conventional antimicrobial therapy.

描述（由申请人提供）：该正在进行的研究项目的长期目标是利用单克隆抗体（mab）生产技术作为更好地了解卡氏疟原虫宿主与寄生虫相互作用的工具。我们对利用被动和主动免疫疗法来预防或治疗卡氏疟原虫肺炎（Pcp）特别感兴趣。在上一次资助期间，我们证明我们生产的一种单克隆抗体具有针对五氯苯酚的显着保护作用。此外，我们已经能够使用该单克隆抗体来鉴定该抗体所识别的“保护性”表位，并鉴定出含有该感兴趣表位的两种卡氏疟原虫抗原（A12 和 KEX1）。根据迄今为止的进展，我们为该项目提出了两个首要目标。我们的首要目标是表征和利用这种保护性抗原-抗体相互作用，以开发预防五氯苯酚的主动和被动免疫。我们的第二个目标是确定使用特异性抗体的被动免疫疗法对主动 Pcp 结果的影响，特别强调抗体对 Pcp 期间肺损伤免疫发病机制的影响。为了实现这两个目标，我们提出以下具体目标： 1) 我们将克隆并表征编码A12多肽的基因的完整cDNA，并确定A12抗原是否定位于P. carinii的表面。 2) 我们将定义使用含有 mab 4F11 识别表位的重组抗原进行主动免疫的免疫原性和功效。 3) 我们将检查被动抗体给药对已建立的 Pcp 的影响。具体来说，我们将定义被动抗体疗法对 Pcp 期间观察到的免疫介导肺损伤的影响。我们还将确定被动抗体疗法与传统抗菌疗法相结合的微生物学效果。

项目成果

期刊论文数量（32）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Neutralization of interferon-gamma exacerbates pneumocystis-driven interstitial pneumonitis after bone marrow transplantation in mice.

小鼠骨髓移植后，干扰素-γ的中和会加剧肺孢子虫引起的间质性肺炎。

DOI：
10.1172/jci119326
发表时间：
1997
期刊：
The Journal of clinical investigation.
影响因子：
0
作者：
Garvy,BA;Gigliotti,F;Harmsen,AG
通讯作者：
Harmsen,AG

Antigenic variation of a major surface glycoprotein of Pneumocystis carinii.

卡氏肺囊虫主要表面糖蛋白的抗原变异。

DOI：
发表时间：
1991
期刊：
The Journal of protozoology
影响因子：
0
作者：
Gigliotti,F
通讯作者：
Gigliotti,F

The relationship between entomological indicators of Aedes aegypti abundance and dengue virus infection.

DOI：
10.1371/journal.pntd.0005429
发表时间：
2017-03
期刊：
PLoS neglected tropical diseases
影响因子：
3.8
作者：
Cromwell EA;Stoddard ST;Barker CM;Van Rie A;Messer WB;Meshnick SR;Morrison AC;Scott TW
通讯作者：
Scott TW

A Pneumocystis carinii group I intron ribozyme that does not require 2' OH groups on its 5' exon mimic for binding to the catalytic core.

卡氏肺囊虫 I 组内含子核酶，其 5 外显子模拟物上不需要 2 OH 基团即可与催化核心结合。