Molecularly Targeted Vaccines for Anthrax
炭疽分子靶向疫苗
基本信息
- 批准号:7187390
- 负责人:
- 金额:$ 101.09万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2003
- 资助国家:美国
- 起止时间:2003-08-15 至 2011-01-31
- 项目状态:已结题
- 来源:
- 关键词:AdherenceAdverse reactionsAerosolsAnimalsAnthrax VaccinesAnthrax diseaseAntibodiesAntibody FormationAntigensBacillus (bacterium)Bacillus anthracis sporeBiological AssayBiological WarfareBiologyBlocking AntibodiesBreathingCell LineCellsComplementDependovirusDevelopmentDoseEngineeringEpitopesEvaluationExhibitsFreund&aposs AdjuvantFutureGenerationsHumanHybridsImmune SeraImmune responseImmunityImmunizationImmunologicsImmunologyIn VitroIndividualInfectionIntramuscularKnowledgeLicensingMolecularMusOryctolagus cuniculusPeptidesPerformancePopulationPrimatesProteinsProtocols documentationRouteSerumSiteStructureSystemTandem Repeat SequencesTestingToxinTreatment ProtocolsVaccinesValidationVirulentVirusanthrax lethal factoranthrax toxinbasedesigndesign and constructiondisorder controledema factorimmunogenicityimprovedin vitro Assayinsightinterestmacrophageneutralizing antibodypreventprototyperesearch studyresponsevaccine evaluation
项目摘要
Inhalation anthrax has emerged as a significant and continuing biowarfare and bioterrofism threat.
Though vaccine strategies have substantially controlled this disease in animal populations, the current
vaccine licensed for human use has several shortcomings including significant adverse reactions and low
immunogenicity resulting in the need for multiple immunizations. The biology of anthrax infection and
specifically the actions of its toxins have been elegantly elucidated at the molecular and cellular level. This
presents a unique opportunity to rationally designed and develop an improved vaccine that can counter
current anthrax as well as modified forms that may be encountered in the future.
In this project we will use the substantial body of knowledge and insight available relating to anthrax toxin
to develop molecularly targeted vaccines to prevent the catastrophic effects of toxin following infection.
Based on careful analysis of the crystal structure, sequence, and functional studies of all components of the
anthrax toxins, we will develop soluble protein vaccines that direct antibody responses towards the critical
protein segments involved in toxin activation, assembly, and adherence to cells. We will test these vaccine
constructs for their ability to elicit strong antibody responses with the ability to neutralize toxin activity in in
vitro assays. Based on analysis of responses to the soluble protein constructs, selected constructs will be
moved into the adeno-associated virus vaccine platform for development of an expression vaccine.
Traditionally such vaccines have exhibited higher immunogenicity and AAV in particular has yielded very
durable responses. The AAV-based vaccines will be tested for immunogenicity and are for the ability to elicit
toxin-neutralizing antibodies, as well as for use in concert with soluble protein immunogens. Finally, the
most promising constructs of both soluble protein and expressed forms will be tested in anthrax spore
inhalation challenge studies in rabbits. Such experiments have been extensively validated against primate
experiments previously and also appear to correlate most closely with human anthrax disease and
protection. Through this approach we will develop promising candidate anthrax vaccines that can protect
against currently existing strains of anthrax as well as new and enhanced threats based on engineered
forms of anthrax.
吸入性炭疽病已成为一种重大的、持续的生物武器和生物毒害威胁。
尽管疫苗策略在很大程度上控制了动物种群中的这种疾病,但目前的
授权人类使用的疫苗有几个缺点,包括严重的不良反应和低
免疫原性导致需要进行多次免疫。炭疽病感染的生物学和
具体地说,其毒素的作用已在分子和细胞水平上得到了优雅的阐明。这
提供了一个独特的机会,可以合理地设计和开发一种可以对抗
目前的炭疽病以及今后可能遇到的改良形式。
在这个项目中,我们将使用与炭疽毒素相关的大量知识和见解
开发分子靶向疫苗,以防止毒素在感染后的灾难性影响。
基于对所有成分的晶体结构、序列和功能的仔细分析
炭疽毒素,我们将开发可溶性蛋白疫苗,将抗体反应定向到关键的
参与毒素激活、组装和与细胞黏附的蛋白质片段。我们将对这些疫苗进行测试
构建其能够诱导强大的抗体反应并中和体内毒素活性的载体
体外试验。基于对可溶蛋白质构建物的响应分析,选定的构建物将是
进入腺相关病毒疫苗平台,开发表达疫苗。
传统上,这种疫苗表现出更高的免疫原性,特别是AAV已经产生了非常
持久的反应。以AAV为基础的疫苗将接受免疫原性测试,并用于诱导
毒素中和抗体,以及与可溶性蛋白免疫原结合使用。最后,
最有希望的可溶性蛋白质和表达形式的构建将在炭疽孢子中进行测试
在兔身上进行的吸入性挑战研究。这样的实验已经在灵长类动物身上得到了广泛的验证
以前的实验也似乎与人类炭疽病和
保护。通过这种方法,我们将开发出有希望的候选炭疽疫苗,这种疫苗可以预防
针对当前存在的炭疽菌株以及基于工程设计的新的和增强的威胁
各种形式的炭疽病。
项目成果
期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Recombinant vaccine displaying the loop-neutralizing determinant from protective antigen completely protects rabbits from experimental inhalation anthrax.
显示来自保护性抗原的环中和决定簇的重组疫苗完全保护兔子免受实验性吸入炭疽的侵害。
- DOI:10.1128/cvi.00612-12
- 发表时间:2013
- 期刊:
- 影响因子:0
- 作者:Oscherwitz,Jon;Yu,Fen;Jacobs,JanaL;Cease,KempB
- 通讯作者:Cease,KempB
Anthrax vaccine recipients lack antibody against the loop neutralizing determinant: A protective neutralizing epitope from Bacillus anthracis protective antigen.
- DOI:10.1016/j.vaccine.2015.03.037
- 发表时间:2015-05-11
- 期刊:
- 影响因子:5.5
- 作者:Oscherwitz J;Quinn CP;Cease KB
- 通讯作者:Cease KB
Epitope-focused peptide immunogens in human use adjuvants protect rabbits from experimental inhalation anthrax.
人用佐剂中的针对表位的肽免疫原可以保护兔子免受实验性吸入性炭疽病的侵害。
- DOI:10.1016/j.vaccine.2014.11.042
- 发表时间:2015
- 期刊:
- 影响因子:5.5
- 作者:Oscherwitz,Jon;Feldman,Daniel;Yu,Fen;Cease,KempB
- 通讯作者:Cease,KempB
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Kemp Bailey Cease其他文献
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{{ truncateString('Kemp Bailey Cease', 18)}}的其他基金
Epitope-specific vaccines targeting the alpha toxin of Staphylococcus aureus
针对金黄色葡萄球菌α毒素的表位特异性疫苗
- 批准号:
8391150 - 财政年份:2010
- 资助金额:
$ 101.09万 - 项目类别:
Epitope-specific vaccines targeting the alpha toxin of Staphylococcus aureus
针对金黄色葡萄球菌α毒素的表位特异性疫苗
- 批准号:
8597331 - 财政年份:2010
- 资助金额:
$ 101.09万 - 项目类别:
Epitope-specific vaccines targeting the alpha toxin of Staphylococcus aureus
针对金黄色葡萄球菌α毒素的表位特异性疫苗
- 批准号:
8212753 - 财政年份:2010
- 资助金额:
$ 101.09万 - 项目类别:
Epitope-specific vaccines targeting the alpha toxin of Staphylococcus aureus
针对金黄色葡萄球菌α毒素的表位特异性疫苗
- 批准号:
8045558 - 财政年份:2010
- 资助金额:
$ 101.09万 - 项目类别:
ADJUVANT STRATEGIES USING T CELL HELP ENHANCER PEPTIDES
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3547529 - 财政年份:1989
- 资助金额:
$ 101.09万 - 项目类别:
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