NOVEL ADENOVIRUS-VECTORED HIV VACCINE THAT KNOCKS THE SOCS1 OFF DENDRITIC CELLS

新型腺病毒载体 HIV 疫苗可敲除树突状细胞上的 SOCS1

• 批准号: 7715852
• 负责人: Jerry L Blackwell
• 金额: $ 6.8万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715852
• 关键词: Adenovirus Vector; Adenoviruses; Antigens; Capsid; Capsid Proteins; Computer Retrieval of Information on Scientific Projects Database; Dendritic Cells; Effectiveness; Epitopes; Funding; Genes; Genetic Transduction; Grant; Humoral Immunities; Immune response; Institution; Pathway interactions; Peptides; Process; Research; Research Personnel; Resources; Source; Transgenes; United States National Institutes of Health; Vaccination; Vaccines; Viral Vector; base; immunogenic; novel; response; vector; vector vaccine; Adenovirus Vector; Adenoviruses; Antigens; Capsid; Capsid Proteins; Computer Retrieval of Information on Scientific Projects Database; Dendritic Cells; Effectiveness; Epitopes; Funding; Genes; Genetic Transduction; Grant; Humoral Immunities; Immune response; Institution; Pathway interactions; Peptides; Process; Research; Research Personnel; Resources; Source; Transgenes; United States National Institutes of Health; Vaccination; Vaccines; Viral Vector; base; immunogenic; novel; response; vector; vector vaccine

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A variety of viral vectors have been employed to accomplish gene-based vaccination. One particularly promising approach is based upon genetic transduction via replication-incompetent adenoviral vectors (Ad). Despite the many potential advantages of Ad vectors for vaccine application, full utility of current Ad vaccines may be limited by the host anti-vector immune response. Specifically, the anti-Ad humoral immunity abrogates the effectiveness of subsequent administrations of the Ad vector, confounding expression of the encoded transgene, and thus practically restricting the gains that might be accrued via booster effect. To exploit the inherent antigenicity of the Ad vector we have developed an approach based on incorporation of the immunizing antigen epitope directly into the Ad capsid. This novel paradigm is based upon Ad presenting the antigen as a component of the capsid rather than an encoded transgene. Incorporation of immunogenic peptides into the Ad capsid offers potential advantages. Most noteworthy, the processing of the capsid incorporated antigen via the exogenous pathway should result in a strong humoral response akin to the response provoked by native Ad capsid proteins. In addition, since anti-Ad capsid responses are augmented by repeated vector administration, immune responses against antigenic epitopes that are part of the Ad capsid should be augmented by repeated administration as well, thus allowing boosting. These considerations suggest that this novel capsid-incorporated antigen approach may offer exciting potentials to realize Ad-based vaccine strategies that circumvent the major limitations associated with Ad vectors.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 已经采用了多种病毒载体来完成基于基因的疫苗接种。 一种特别有前途的方法是基于通过不含复制的腺病毒载体（AD）的遗传转导。 尽管AD载体用于疫苗的应用有许多潜在的优势，但当前AD疫苗的全部效用可能受到宿主抗载体免疫反应的限制。 具体而言，抗AD的体液免疫消除了随后的AD向量施用的有效性，使编码转基因的表达混淆，因此实际上限制了通过增强作用可能产生的收益。 为了利用AD载体的固有抗原性，我们开发了一种基于将免疫表位的掺入直接掺入AD CAPSID中的方法。这个新颖的范式基于AD呈现抗原作为衣壳的组成部分，而不是编码的转基因。 将免疫原性肽掺入AD CAPSID中提供了潜在的优势。 最值得注意的是，在外源途径中加工带状的抗原应导致强烈的体液反应，类似于天然AD Capsid蛋白引起的反应。 此外，由于反复给药可增强抗AD CAPSID响应，因此也应重复给药增强对AD CAPSID一部分的抗原表位的免疫反应，从而可以增强。 这些考虑因素表明，这种新颖的结合木质抗原方法可能会提供令人兴奋的潜力，以实现基于AD的疫苗策略，以规避与AD载体相关的主要局限性。