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Evaluation of Protective Immunity After Mucosal Vaccination Against Ebola Virus

埃博拉病毒粘膜疫苗接种后的保护性免疫评价

基本信息

批准号：
8312627
负责人：
Maria A Croyle
金额：
$ 61.84万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-05-15 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8312627
关键词：
Address Adenoviruses Adjuvant Animal Model Antigens B-Lymphocytes Biochemical Biological Bioterrorism CD8B1 gene Capsid Cavia Childhood Clinical Clinical Data Communicable Diseases Data Development Dose Dose-Limiting Drug Formulations Ebola Vaccines Ebola virus Elements Evaluation Exposure to Face Filovirus Gastrointestinal tract structure Glycoproteins Goals Human Immune response Immune system Immunity Immunization Infection Influenza A Virus, H5N1 Subtype Lead Light Memory Methods Modeling Modification Mucosal Immune Responses Mucosal Immunity Mus Nature Nose Oral Oral Administration Play Population Protocols documentation Recombinants Regimen Respiratory System Respiratory tract structure Role Route SARS coronavirus Screening procedure Serotyping System T memory cell T-Lymphocyte Testing Toxic effect Ursidae Family Vaccination Vaccines Vesicular stomatitis Indiana virus Viral base cell mediated immune response design mucosal vaccination nonhuman primate pathogen protective efficacy response vaccination strategy vaccine development vector

项目摘要

DESCRIPTION (provided by applicant): World globalization and the increased threat of bioterrorism have mandated rapid evaluation of immunization strategies for a panel of agents including Ebola (EBO), SARS and H5N1 viruses for which there are limited clinical or biological data. To date, the most effective Ebola immunization protocols have involved parenteral administration of a vesicular stomatitis virus (VSV)-based vector expressing the Ebola glycoprotein (EBOGP) or administration of recombinant adenovirus serotype 5 (Ad) expressing EBOGP. Although Ad vaccine carriers have a substantial amount of clinical data to support their use, they face the problem of widespread pre-existing immunity in the human population. To date, vaccination strategies against EBO involve use of Ad as the vaccine carrier but do not address this important issue. Studies proposed have three major aims employing Ad as a model vaccine carrier and EBOGP as a model antigen. We plan to test the hypothesis that mucosal administration (oral or nasal) can circumvent pre-existing immunity against Ad and confer immunity against Ebola challenge in several animal models. Mucosal immunization against EBO and other filoviruses has not been explored, yet immunization through the respiratory and gastrointestinal tract can effectively induce both local and systemic immune responses against many pathogens. Although there is some suggestive evidence that mucosal immunity plays a significant role in protection from EBO challenge, it is not clear what the influence of both the innate and adaptive immune response and the interaction between the two bears on the efficacy of EBO immunization strategies. Studies detailed in this proposal are specifically designed to fully characterize T and B cell mediated immune responses that develop systemically and locally after mucosal immunization before and after challenge with EBO in the presence and absence of pre-existing immunity to the Ad carrier. We also propose several formulation and biochemical strategies to promote and further strengthen the immune response against EBOGP during mucosal immunization. Results from these studies will further the understanding of EBO infection and identify specific elements of the immune response necessary to confer immunity to EBO. This information will be of value in the development of immunization strategies and identify targets for anti-viral regimens. They will also lead to development of effective and attractive vaccination strategies that can be applied to other pathogens.

描述（由申请人提供）：世界全球化和生物恐怖主义威胁的增加要求对包括埃博拉 (EBO)、SARS 和 H5N1 病毒在内的一组病原体的免疫策略进行快速评估，这些病毒的临床或生物学数据有限。迄今为止，最有效的埃博拉免疫方案涉及肠胃外施用表达埃博拉糖蛋白（EBOGP）的水泡性口炎病毒（VSV）载体或施用表达EBOGP的重组腺病毒血清型5（Ad）。尽管Ad疫苗携带者有大量的临床数据支持其使用，但他们面临着人群中广泛存在的预先存在的免疫力的问题。迄今为止，针对 EBO 的疫苗接种策略涉及使用 Ad 作为疫苗载体，但没有解决这个重要问题。拟议的研究有三个主要目标，采用 Ad 作为模型疫苗载体和 EBOGP 作为模型抗原。我们计划测试以下假设：粘膜给药（口服或鼻腔）可以规避预先存在的针对 Ad 的免疫力，并在几种动物模型中赋予针对埃博拉病毒的免疫力。针对 EBO 和其他丝状病毒的粘膜免疫尚未被探索，但通过呼吸道和胃肠道的免疫可以有效诱导针对许多病原体的局部和全身免疫反应。尽管有一些提示性证据表明粘膜免疫在抵御 EBO 攻击方面发挥着重要作用，但尚不清楚先天性免疫反应和适应性免疫反应以及两者之间的相互作用对 EBO 免疫策略的功效有何影响。该提案中详述的研究专门设计用于充分表征 T 和 B 细胞介导的免疫反应，这些免疫反应是在存在和不存在针对 Ad 载体的预先存在的免疫力的情况下，在 EBO 攻击之前和之后进行粘膜免疫后系统和局部产生的。我们还提出了几种制剂和生化策略，以促进和进一步加强粘膜免疫过程中针对 EBOGP 的免疫反应。这些研究的结果将进一步了解 EBO 感染，并确定赋予 EBO 免疫力所需的免疫反应的特定要素。这些信息对于制定免疫策略和确定抗病毒方案的目标具有重要价值。它们还将导致开发出可应用于其他病原体的有效且有吸引力的疫苗接种策略。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A Single Dose Respiratory Recombinant Adenovirus-Based Vaccine Provides Long-Term Protection for Non-Human Primates from Lethal Ebola Infection.

DOI：
10.1021/mp500646d
发表时间：
2015-08-03
期刊：
Molecular pharmaceutics
影响因子：
4.9
作者：
Choi JH;Jonsson-Schmunk K;Qiu X;Shedlock DJ;Strong J;Xu JX;Michie KL;Audet J;Fernando L;Myers MJ;Weiner D;Bajrovic I;Tran LQ;Wong G;Bello A;Kobinger GP;Schafer SC;Croyle MA
通讯作者：
Croyle MA

Evaluation of Different Strategies for Post-Exposure Treatment of Ebola Virus Infection in Rodents.

啮齿类动物埃博拉病毒感染暴露后治疗不同策略的评估。

DOI：
10.4172/2157-2526.s1-007
发表时间：
2011
期刊：
Journal of bioterrorism & biodefense
影响因子：
0
作者：
Richardson,JasonS;Wong,Gary;Pillet,Stéphane;Schindle,Samantha;Ennis,Jane;Turner,Jeffrey;Strong,JamesE;Kobinger,GaryP
通讯作者：
Kobinger,GaryP

Immunization and Drug Metabolizing Enzymes: Focus on Hepatic Cytochrome P450 3A.