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

基本信息

  • 批准号:
    8212753
  • 负责人:
  • 金额:
    --
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-10-01 至 2014-09-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Staphylococcus aureus has become a multifaceted threat faced in our hospitals, our nursing homes, and increasingly, in our communities. In particular, methicillin-resistant S. aureus (MRSA) has been an increasing problem in each of these venues, and resistance to other antibiotics, including varying degrees of resistance to vancomycin, is increasingly complicating management of S. aureus infections. The goal of this project is to develop epitope-specific vaccines targeting alpha toxin and the phenol-soluble modulins (PSMs), which are two critical virulence factors for S. aureus, for use in preventing S. aureus infections. Antibody neutralizing determinants will be identified in alpha toxin and the PSMs through screening of peptide sequences in vivo in the mouse model. Multiple antigenic peptides (MAPs) containing universal heterologous helper T cell epitopes or autologous helper T cell epitopes identified from alpha toxin, colinearly-linked to the neutralizing B cell determinants, will then be screened for efficacy in the murine pneumonia and cutaneous abscess challenge models employing virulent alpha toxin- and PSM-producing MRSA. Immune correlates of protection, including antibody and toxin neutralizing titer and antibody affinity, will be assessed in vitro and used to model vaccine-related efficacy in preventing morbidity and mortality from S. aureus infections in mice. Following a rigorous evaluation of vaccine safety in the murine model, MAP vaccines will be validated for immunogenicity in outbred rabbits using human use adjuvants, and the rabbit antisera will be evaluated for protective efficacy using passive transfer protocols in the mouse models of S. aureus infection, as a prelude to further clinical testing in nonhuman primates. PUBLIC HEALTH RELEVANCE: Staphylococcus aureus has become a multifaceted threat that confronts us in war and peace. It is present on the battlefield, in our hospitals, our nursing homes, and our communities, turning lesser injuries and illnesses into life-altering catastrophes. It is becoming increasingly resistant to our antibiotics, and is escaping our control measures. The goal of this project is to provide the VA, and society at large, with a new tool and a new approach for countering the human and financial burden of S. aureus infections by developing a vaccine that targets two critical virulence factors, alpha-toxin and the phenol-soluble modulins. This work may lead to a safe and effective virulence factor-specific S. aureus vaccine that could broadly benefit the veteran and non-veteran population, and may facilitate the development of other virulence factor vaccines.
描述(由申请人提供): 金黄色葡萄球菌已经成为我们医院、疗养院以及越来越多的社区面临的一个多方面的威胁。特别是,耐甲氧西林金黄色葡萄球菌(MRSA)在这些场所都是一个日益严重的问题,对其他抗生素的耐药性,包括对万古霉素的不同程度的耐药性,正日益使金黄色葡萄球菌感染的管理复杂化。该项目的目标是开发针对α毒素和苯酚可溶性调制素(PSM)的表位特异性疫苗,这两个因子是金黄色葡萄球菌的两个关键毒力因子,用于预防金黄色葡萄球菌感染。在小鼠模型中,通过筛选体内的多肽序列,将在阿尔法毒素和PSM中鉴定抗体中和决定因素。多个抗原肽(MAP)包含从α毒素中鉴定的通用异源辅助T细胞表位或自体辅助T细胞表位,并与中和B细胞决定簇共线连接,然后将在使用产生毒力的α毒素和PSM的MRSA的小鼠肺炎和皮肤脓肿攻击模型中筛选有效性。保护的免疫相关性,包括抗体和毒素中和效价以及抗体亲和力,将在体外进行评估,并用于模拟疫苗相关的有效性,以防止金黄色葡萄球菌感染小鼠的发病率和死亡率。在对小鼠模型中的疫苗安全性进行严格评估后,将使用人类使用的佐剂验证MAP疫苗在杂交兔子中的免疫原性,并将在金黄色葡萄球菌感染的小鼠模型中使用被动转移方案评估兔抗血清的保护效果,作为在非人类灵长类动物中进行进一步临床测试的前奏。 公共卫生相关性: 金黄色葡萄球菌已经成为我们在战争与和平中面临的多方面威胁。它出现在战场上,出现在我们的医院、疗养院和社区中,将较小的伤害和疾病转变为改变生活的灾难。它对我们的抗生素越来越耐药,并正在逃避我们的控制措施。该项目的目标是为退伍军人管理局和整个社会提供一种新工具和新方法,通过开发一种针对两种关键毒力因子--阿尔法毒素和苯酚可溶性调节素--的疫苗来对抗金黄色葡萄球菌感染带来的人类和经济负担。这项工作可能导致一种安全有效的毒力因子特异性金黄色葡萄球菌疫苗,可广泛惠及退伍军人和非退伍军人,并可能促进其他毒力因子疫苗的开发。

项目成果

期刊论文数量(0)
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Kemp Bailey Cease其他文献

Kemp Bailey Cease的其他文献

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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:
    --
  • 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:
    --
  • 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:
    --
  • 项目类别:
Molecularly Targeted Vaccines for Anthrax
炭疽分子靶向疫苗
  • 批准号:
    7187390
  • 财政年份:
    2003
  • 资助金额:
    --
  • 项目类别:
Molecularly Targeted Vaccines for Anthrax
炭疽分子靶向疫苗
  • 批准号:
    7025796
  • 财政年份:
    2003
  • 资助金额:
    --
  • 项目类别:
Molecularly Targeted Vaccines for Anthrax
炭疽分子靶向疫苗
  • 批准号:
    6787799
  • 财政年份:
    2003
  • 资助金额:
    --
  • 项目类别:
Molecularly Targeted Vaccines for Anthrax
炭疽分子靶向疫苗
  • 批准号:
    6838737
  • 财政年份:
    2003
  • 资助金额:
    --
  • 项目类别:
Molecularly Targeted Vaccines for Anthrax
炭疽分子靶向疫苗
  • 批准号:
    6690634
  • 财政年份:
    2003
  • 资助金额:
    --
  • 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:
    --
  • 项目类别:
RATIONAL PEPTIDE COMPONENT VACCINES FOR AIDS
艾滋病合理肽成分疫苗
  • 批准号:
    3140806
  • 财政年份:
    1989
  • 资助金额:
    --
  • 项目类别:

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