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.
吸入性炭疽已成为一种重大和持续的生物战和生物恐怖主义威胁。
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
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
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
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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
使用 T 细胞帮助增强肽的佐剂策略
- 批准号:
3547529 - 财政年份:1989
- 资助金额:
$ 101.09万 - 项目类别:
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