Human Immunity to Vaccinia Virus

目前的政策，以保护美国人免受天花授权免疫naTve和以前 用活疫苗病毒（VV）接种的成年人。对W的适应性免疫的知识仅限于 中和抗体、细胞毒性T淋巴细胞（CTL）活性和淋巴细胞增殖的描述 这主要是因为在当前的分子免疫学时代之前，广泛的疫苗接种已经停止。 该项目的研究将检查新接种疫苗和再接种疫苗的W特异性记忆T细胞的进化。 （成人）成人。W特异性获得性免疫与病毒载量及先天免疫的关系 将结合项目7和项目9确定豁免。具体目标是： 1.鉴定诱导CD 8 <$T细胞记忆的免疫显性VV表位。人工神经网络和 计算算法将首先用于选择肽表位，然后评估肽表位。 结合HLA I类等位基因和评估的能力，肽刺激IFN-？和IL-2应答 HLA匹配和HLA不匹配的初次接种者和给予W. 2.在适应性免疫的诱导和记忆阶段确定CD 8？细胞的功能表型 免疫力W。HLA I类四聚体-肽复合物将用于鉴定和定量CD 8 ~+细胞 在接种前和接种后9天、6、12和24个月携带对W表位特异的TCR。 产生假定免疫介质的淋巴细胞（IFN-？，穿孔素，MIP-lcc）和方位记忆 将在初次接种者中前瞻性评价标志物（CD 45 RO、CD 45 RA、CCR 7），并加强免疫 成年人了 3.评价初次接种和加强免疫后Vv特异性CD 8+细胞的克隆型库 以前接种过疫苗的成年人。TCR V13的使用和CDR 3长度和序列多态性将被评估。 在选定的HLA-A2+和HLA-A11+个体中进行前瞻性评价。

Current policy to protect Americans against smallpox mandates immunization of naTve and previously vaccinated adults with live vaccinla virus (VV). Knowledge of adaptive immunity to W is limited to descriptions of neutralizing antibodies, cytotoxic T lymphocyte (CTL) activity, and lymphocyte proliferation responses, largely because widespread vaccination ceased before the current era of molecular immunology. Research in this project will examine the evolution of W-specific memory T cells in newly vaccinated and revaccinated (boosted) adults. The relationship of W-specific adaptive immunity to viral load and innate immunity will be determined in conjunction with projects 7 and 9. The specific aims are to: 1. Identify immunodominant VV epitopes that induce CD8 ¿ T cell memory. Artificial neural networks and computational algorithms will initially be used to select peptide epitopes, followed by evaluation of peptide binding to HLA class I alleles and assessment of the ability of peptides to stimulate IFN-? and IL-2 responses by HLA-matched and HLA-mismatched primary vaccinees and adults given booster doses of W. 2. Determine the functional phenotype of CD8 ¿ cells during the inductive and memory phases of adaptive immunity to W. HLA class I tetramer-peptide complexes will be used to identify and quantify CD8 ¿ cells bearing TCR specific for W epitopes before vaccination and 9 days, 6, 12, and 24 months post-vaccination. Lymphocytes producing putative mediators of immunity (IFN-?, perforin, MIP-lcc) and bearing memory markers (CD45RO, CD45RA, CCR7) will be evaluated prospectively in primary vaccinees and boosted adults. 3. Evaluate the clonotypic repertoire of Vv-specific CD8 ¿ cells following primary vaccination and boosting of previously vaccinated adults. TCR VI3 usage and CDR3 length and sequence polymorphism will be evaluated prospectively in selected HLA-A2+ and HLA-A11+ individuals.