IMMUNE CONTROL OF CAE LENTIVIRUS
CAE 慢病毒的免疫控制
基本信息
- 批准号:6632626
- 负责人:
- 金额:$ 13.78万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1995
- 资助国家:美国
- 起止时间:1995-09-30 至 2006-05-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Vaccination trials were conducted in outbred Saanen goats using recombinant vaccinia or plasmid DNA vectors expressing the caprine arthritis-encephalitis virus (CAEV) env gene or plasmid DNA expressing CAEV env and tat. Intradermal vaccination with plasmid DNA induced biased type 1 immune responses to vector encoded surface envelope (SU), whereas vaccinia induced type 2 responses. Subcutaneous boost with purified SU in Freund's incomplete adjuvant specifically expanded type 1 or type 2 memory established by initial immunizations with plasmid DNA or vaccinia. These goats together with sham vaccinated and non-vaccinated control goats were challenged intravenously with a molecular clone of tissue culture amplified CAEV. Preliminary results through 24 weeks postchallenge indicate that virus replication is restricted by type 1 immunity induced by plasmid DNA but not by type 2 responses induced by vaccinia. These data provide a basis to determine the role of qualitatively distinct immune responses to lentiviral SU in control of virus replication and disease progression. Therefore, the first objective of this proposal is to test the hypothesis that type 1 immunity induced by plasmid DNA restricts virus replication and prevents development of arthritis following CAEV challenge, whereas type 2 immunity induced by recombinant vaccinia fails to control virus replication and promotes development of arthritis. Proposed experimants expand the preliminary studies to a larger number of animals required for significant evaluation of virus load and disease progression. In addition, the challenge inoculum will be wild type virus derived from field cases of CAE arthritis. Additional goats were co- immunized with plasmid DNA expressing CAEV env with or without tat together with a second plasmid DNA encoding caprine interferon gamma (IFN). These studies provide preliminary evidence that synergistic effects of plasmid encoded Tat and IFN inhibit primary adaptive B cell responses to plasmid encoded SU without effect on activation of SU responsive Th1 lymphocytes. Significant control of CAEV replication by goats with this vaccine induced immunologic profile will support further studies on the role of Tat and IFN as vaccine components. Therefore, the second objective of this proposal is to evaluate virus replication following CAEV challenge of goats co-immunized with plasmid DNA expressing CAEV env and tat genes and caprine IFN.
使用表达山羊关节炎-脑炎病毒(CAEV)env基因的重组牛痘或质粒DNA载体或表达CAEV env和达特的质粒DNA在远交种萨宁山羊中进行疫苗接种试验。 皮内接种质粒DNA诱导偏向载体编码的表面包膜(SU)的1型免疫应答,而牛痘诱导2型应答。 用弗氏不完全佐剂中的纯化SU皮下加强特异性扩增通过用质粒DNA或牛痘初始免疫建立的1型或2型记忆。 用组织培养扩增的CAEV分子克隆对这些山羊以及假疫苗接种和未接种的对照山羊进行静脉内攻击。 攻毒后24周的初步结果表明,病毒复制受到质粒DNA诱导的1型免疫的限制,但不受牛痘诱导的2型反应的限制。 这些数据提供了一个基础,以确定定性不同的免疫反应慢病毒SU在控制病毒复制和疾病进展的作用。 因此,本提案的第一个目的是检验以下假设:质粒DNA诱导的1型免疫限制病毒复制并防止CAEV攻击后关节炎的发展,而重组牛痘诱导的2型免疫不能控制病毒复制并促进关节炎的发展。 拟议的实验者将初步研究扩展到显著评价病毒载量和疾病进展所需的大量动物。 此外,攻毒接种物将是来自CAE关节炎田间病例的野生型病毒。 将另外的山羊用表达CAEV env(具有或不具有达特)的质粒DNA与编码山羊干扰素γ(IFN)的第二质粒DNA共同免疫。 这些研究提供了初步证据,即质粒编码的达特和IFN的协同作用抑制了原代适应性B细胞对质粒编码的SU的应答,而不影响SU应答性Th 1淋巴细胞的活化。用该疫苗诱导的免疫学特征显著控制山羊CAEV复制将支持进一步研究达特和IFN作为疫苗组分的作用。 因此,本建议的第二个目的是评价用表达CAEV env和达特基因的质粒DNA和山羊IFN共免疫山羊后CAEV攻击的病毒复制。
项目成果
期刊论文数量(0)
专著数量(0)
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WILLIAM P CHEEVERS其他文献
WILLIAM P CHEEVERS的其他文献
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{{ truncateString('WILLIAM P CHEEVERS', 18)}}的其他基金
CYTOKINE MODULATION OF LENTIVIRAL DNA VACCINES
慢病毒 DNA 疫苗的细胞因子调节
- 批准号:
2878029 - 财政年份:1997
- 资助金额:
$ 13.78万 - 项目类别:
CYTOKINE MODULATION OF LENTIVIRAL DNA VACCINES
慢病毒 DNA 疫苗的细胞因子调节
- 批准号:
2555244 - 财政年份:1997
- 资助金额:
$ 13.78万 - 项目类别:
PATHOGENESIS OF RETROVIRUS INDUCED ARTHRITIS
逆转录病毒引起的关节炎的发病机制
- 批准号:
3155553 - 财政年份:1981
- 资助金额:
$ 13.78万 - 项目类别:
PATHOGENESIS OF RETROVIRUS INDUCED ARTHRITIS
逆转录病毒引起的关节炎的发病机制
- 批准号:
3155561 - 财政年份:1981
- 资助金额:
$ 13.78万 - 项目类别:
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