MIMOTOPE CONVERSION OF HIV-1 CARBOHYDRATE ANTIGENS

HIV-1 碳水化合物抗原的同位素转化

• 批准号: 6312480
• 负责人: THOMAS KIEBER-EMMONS
• 金额: $ 37.16万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2002-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6312480
• 关键词: AIDS vaccines; HIV envelope protein gp120; HIV envelope protein gp160; antigen antibody reaction; biomimetics; carbohydrates; cellular immunity; complement pathway; enzyme linked immunosorbent assay; glycoproteins; human immunodeficiency virus 1; human tissue; humoral immunity; immunoglobulin A; immunoglobulin G; immunoglobulin M; laboratory mouse; peptide chemical synthesis; serology /serodiagnosis; surface antigens; synthetic vaccines; vaccine development

DESCRIPTION: (Adapted from Applicant's Abstract) Carbohydrate antigens have been the basis for eliciting protective immune responses against many pathogens, yet this approach has not been adequately assessed in HIV research. Targeting carbohydrates could present new possibilities for group specific vaccine development because they are present on all isolates. Furthermore, anti-carbohydrate antibodies may sensitize HIV infected cells for complement-mediated cytolysis by targeting cell surface expressed glycoprotein. We have developed a program concerned with the interconversion of carbohydrate epitopes associated with HIV into a peptide-based vaccine strategy to augment carbohydrate cross-reactive systemic and mucosal responses. We have shown that peptides can induce carbohydrate cross-reactive IgM and IgG responses that can be further manipulated to participate in lysing HIV infected cells or target HIV virions. This proposal has three specific aims: 1) To further refine peptide mimotopes of HIV associated carbohydrate antigens. We evaluate the antigenic mimicry of peptide mimotopes by kinetic and binding parameters of peptides that compete with HIV associated carbohydrates for Con A and anti- carbohydrate antibody using BIACORE and ELISA analysis. 2) To evaluate mechanisms to enhance or augment immune responses to HIV-1 associated carbohydrates. Serological comparisons are made between peptide, carbohydrate conjugates and mimotope encoded DNA immunizations. 3.) To determine the extent to which priming and boosting strategies lead to enhanced carbohydrate cross-reactive systemic and mucosal anti-HIV antibody responses. Focus is placed on the ability to prime for an antibody response to envelope expressed carbohydrate and to have this response boosted with later injections of HIV-1 protein, carbohydrate-conjugates or carbohydrate expressing cells. Based upon preliminary evidence it is hypothesized that boosting will further augment or enhance carbohydrate cross-reactive IgG2a, IgA, and secretory IgM responses. Incorporation of encoded peptide mimotopes with HIV CTL epitopes into a DNA vaccine strategy further ensures HIV memory responses and augmented T cell immunity that can target infected cells. This is a unique approach using both antibodies and T cells to target infected cells. This approach could set the groundwork for further development, providing a novel strategy to supplement HIV vaccine research.

描述：(摘自申请者摘要)碳水化合物抗原有 是激发保护性免疫反应的基础 然而，这种方法在艾滋病毒研究中还没有得到充分的评估。 以碳水化合物为靶点可能为特定群体提供新的可能性 疫苗开发，因为它们存在于所有分离株上。此外， 抗碳水化合物抗体可能会使HIV感染细胞对 补体通过靶向细胞表面表达的糖蛋白介导的细胞溶解。 我们已经开发了一个与碳水化合物相互转化有关的程序 将HIV相关表位转化为基于多肽的疫苗策略以增强 碳水化合物对全身和粘膜的交叉反应。我们已经证明了 多肽可以诱导碳水化合物交叉反应的IgM和IgG反应，从而 被进一步操纵以参与裂解HIV感染细胞或靶点 艾滋病毒病毒粒子。这项建议有三个具体目标：1)进一步完善 HIV相关碳水化合物抗原的多肽模拟表位。我们评估了 用动力学参数和结合参数模拟多肽模拟表位 与HIV相关碳水化合物竞争ConA和抗-DNA的多肽 用Biacore和酶联免疫吸附试验检测糖类抗体。2)评估 增强或增强对HIV-1相关免疫反应的机制 碳水化合物。对多肽、碳水化合物进行了血清学比较 结合物和模拟表位编码DNA免疫。3.)确定范围的步骤 启动和增强策略会导致碳水化合物增加 全身和粘膜抗HIV抗体的交叉反应。重点是 依赖于对表达的包膜的抗体反应的启动能力 碳水化合物，并通过以后注射HIV-1来增强这种反应 蛋白质、碳水化合物结合物或碳水化合物表达细胞。基于 初步证据表明，假定助推将进一步扩大或 增强碳水化合物交叉反应的IgG2a、IgA和分泌型IgM反应。 人类免疫缺陷病毒CTL表位的编码多肽模拟表位与DNA的融合 疫苗策略进一步确保艾滋病毒记忆反应和增强的T细胞 可以针对受感染细胞的免疫力。这是一种独特的方法，既使用了 抗体和T细胞以感染细胞为靶点。这种方法可能会设置 为进一步发展奠定基础，提供一种新的战略来补充 艾滋病疫苗研究。

项目成果

Targeting carbohydrate antigens in HIV vaccine development.

HIV 疫苗开发中的靶向碳水化合物抗原。

• DOI: 10.1016/j.vaccine.2005.01.045
• 发表时间: 2005
• 期刊: Vaccine.
• 作者: Pashov,Anastas;Canziani,Gabriela;Macleod,Stewart;Plaxco,Jason;Monzavi-Karbassi,Behjatolah;Kieber-Emmons,Thomas
• 通讯作者: Kieber-Emmons,Thomas

Defining carbohydrate antigens as HIV vaccine candidates.

将碳水化合物抗原定义为艾滋病毒候选疫苗。

• DOI: 10.2174/138161207779313678
• 发表时间: 2007
• 期刊: Current pharmaceutical design
• 影响因子: 3.1
• 作者: Pashov,Anastas;Perry,Marty;Dyar,Michael;Chow,Marie;Kieber-Emmons,Thomas
• 通讯作者: Kieber-Emmons,Thomas

Priming characteristics of peptide mimotopes of carbohydrate antigens.

碳水化合物抗原的肽模拟表位的引发特征。

• DOI: 10.1016/s0264-410x(02)00703-x
• 发表时间: 2003
• 期刊: Vaccine
• 影响因子: 5.5
• 作者: Monzavi-Karbassi,Behjatolah;Shamloo,Shahram;Kieber-Emmons,Matthew;Jousheghany,Fariba;Luo,Ping;Lin,KaityY;Cunto-Amesty,Gina;Weiner,DavidB;Kieber-Emmons,Thomas
• 通讯作者: Kieber-Emmons,Thomas

Antigenic properties of peptide mimotopes of HIV-1-associated carbohydrate antigens.

HIV-1相关碳水化合物抗原的肽模拟表位的抗原特性。

• DOI: 10.1074/jbc.m502964200
• 发表时间: 2005
• 期刊: The Journal of biological chemistry
• 作者: Pashov,Anastas;Canziani,Gabriela;Monzavi-Karbassi,Behjatolah;Kaveri,SriniV;Macleod,Stewart;Saha,Rinku;Perry,Marty;Vancott,ThomasC;Kieber-Emmons,Thomas
• 通讯作者: Kieber-Emmons,Thomas

Concanavalin A binding to HIV envelope protein is less sensitive to mutations in glycosylation sites than monoclonal antibody 2G12.

与单克隆抗体 2G12 相比，伴刀豆球蛋白 A 与 HIV 包膜蛋白的结合对糖基化位点的突变不太敏感。

• DOI: 10.1093/glycob/cwi083
• 发表时间: 2005
• 期刊: Glycobiology
• 影响因子: 4.3
• 作者: Pashov,Anastas;MacLeod,Stewart;Saha,Rinku;Perry,Marty;VanCott,ThomasC;Kieber-Emmons,Thomas
• 通讯作者: Kieber-Emmons,Thomas