Enhancement of mucosal antibody responses to HIV vaccine

增强 HIV 疫苗的粘膜抗体反应

• 批准号: 7677942
• 负责人: Jadranka Bozja
• 金额: $ 30万
• 依托单位: ZETRA BIOLOGICALS, LLC
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7677942
• 关键词: AIDS Vaccines; AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Address; Adjuvant; Adult; Agreement; Animals; Antibodies; Antibody Formation; Antigen-Presenting Cells; Antigens; Cavia; Cellular Immunity; Child; Communicable Diseases; Cytoplasmic Tail; Data; Developed Countries; Developing Countries; Development; Disease; Epitopes; Flagellin; Genetic Variation; Goals; HIV; HIV Infections; HIV vaccine; HIV-1; HIV-1 vaccine; Health; Immune; Immune response; Immunity; Immunization; Immunoglobulin A; Immunoglobulin G; Infection; Intramuscular; Lead; Legal patent; Licensing; Life; Ligands; Medical; Membrane; Membrane Glycoproteins; Methods; Modeling; Molecular; Mucosal Immune Responses; Mucous Membrane; Natural Immunity; Nature; Pattern; Pattern recognition receptor; Peptide Signal Sequences; Phase; Prevalence; Prevention; Preventive; Process; Production; Proteins; Protocols documentation; Quality Control; Research; Research Personnel; SIV; Salmonella; Serum; Site; T-Lymphocyte; Technology; Testing; Toll-Like Receptor 5; Toll-like receptors; Universities; Upper arm; Vaccines; Viral; Virus; Virus-like particle; Work; base; chemokine; cytokine; design; effective therapy; env Gene Products; env Glycoproteins; fighting; gag Gene Products; immunogenicity; influenzavirus; neutralizing antibody; novel; outcome forecast; pandemic disease; pathogen; preclinical study; prophylactic; public health relevance; response; vaccine candidate

DESCRIPTION (provided by applicant): Since 1981, when HIV was first recognized as a serious and deadly disease, the number of infected people has risen to nearly 60 million. There are approximately 14,000 new HIV infections per day, and the WHO predicts that HIV poses the greatest threat to global health in the coming years. Having already claimed more than 20 million lives, HIV/AIDS still remains a largely unmet medical need. The severe nature and poor prognosis associated with this disease, together with high global prevalence and lack of simple and effective treatment, have driven demand for prophylactic vaccines against HIV. As it is the case with other infectious diseases, a safe, effective and available preventive vaccine will ultimately be the preferred method in our fight to end the HIV pandemic. Although developing an effective HIV vaccine remains one of the highest priorities, it also presents formidable scientific challenges to researchers. Currently, there are no HIV vaccines available. Zetra Biologicals, LLC has exclusively licensed novel platform technology from Emory University for vaccine discovery, development and production. Recent data, produced by using our patent protected and patent pending technology, demonstrated that chimeric virus-like particle vaccine candidates elicit strong innate and acquired immune responses. In pre-clinical studies with an early vaccine candidate we have demonstrated a broad antibody and T-cell responses against HIV-1. In Phase I of this project we are planning to leverage our expertise in creating novel HIV vaccine candidates and capabilities of our platform chimeric virus-like particle technology to further develop new HIV vaccine candidates. Our objective is to create chimeric VLPs with membrane-anchored toll-like receptor ligands as a novel HIV-1 vaccine candidate with a goal to elicit broadly anti-HIV neutralizing antibodies and strong mucosal immune responses. The specific aims of the Phase I project are: 1) To produce chimeric virus-like particles (cVLPs) incorporating HIV glycoproteins and membrane-anchored adjuvant molecules; 2) To evaluate the immunogenicity of novel HIV chimeric VLPs in comparison to standard VLPs containing Env and Gag proteins. PUBLIC HEALTH RELEVANCE: More than 60 million people have been infected with the HIV virus, and AIDS has taken the lives of more than 20 million adults and children. With 14,000 new HIV infections every day, HIV continues to spread. Our recent studies on HIV-1 and SIV demonstrated that vaccines produced by using our novel platform technology can offer an alternative strategy for development of an effective, safe, and affordable HIV vaccine. In the proposed project, we will demonstrate that novel chimeric virus-like particles with an incorporated toll-like receptor ligand will induce and enhance immune responses against the HIV-1 virus.

描述（由申请人提供）：自1981年艾滋病毒首次被认为是一种严重和致命的疾病以来，感染人数已上升到近6000万。每天大约有14000人感染艾滋病毒，世界卫生组织预测，艾滋病毒在未来几年将对全球健康构成最大威胁。艾滋病毒/艾滋病已经夺去了2 000多万人的生命，它在很大程度上仍然是一个未得到满足的医疗需求。这种疾病的严重性质和预后差，加上全球流行率高和缺乏简单有效的治疗方法，推动了对艾滋病毒预防性疫苗的需求。与其他传染病的情况一样，一种安全、有效和可获得的预防性疫苗最终将是我们结束艾滋病毒大流行的斗争的首选方法。尽管开发有效的艾滋病毒疫苗仍然是最优先事项之一，但它也给研究人员带来了巨大的科学挑战。目前还没有艾滋病毒疫苗。Zetra Biologicals， LLC独家从Emory大学获得疫苗发现、开发和生产的新平台技术许可。使用我们的专利保护技术和正在申请专利的技术产生的最新数据表明，嵌合病毒样颗粒候选疫苗可引起强烈的先天和获得性免疫反应。在早期候选疫苗的临床前研究中，我们已经证明了针对HIV-1的广泛抗体和t细胞反应。在该项目的第一阶段，我们计划利用我们在创造新型艾滋病毒候选疫苗方面的专业知识和我们平台嵌合病毒样颗粒技术的能力，进一步开发新的艾滋病毒候选疫苗。我们的目标是创建具有膜锚定toll样受体配体的嵌合VLPs，作为一种新的HIV-1候选疫苗，其目标是引发广泛的抗hiv中和抗体和强烈的粘膜免疫反应。I期项目的具体目标是：1)生产含有HIV糖蛋白和膜锚定佐剂分子的嵌合病毒样颗粒（cVLPs）；2)比较新型HIV嵌合VLPs与含有Env和Gag蛋白的标准VLPs的免疫原性。公共卫生相关性：6 000多万人感染了艾滋病毒，2 000多万成人和儿童死于艾滋病。每天新增1.4万例艾滋病毒感染，艾滋病毒继续蔓延。我们最近对HIV-1和SIV的研究表明，使用我们的新平台技术生产的疫苗可以为开发有效、安全和负担得起的HIV疫苗提供另一种策略。在拟议的项目中，我们将证明新型嵌合病毒样颗粒结合toll样受体配体将诱导和增强对HIV-1病毒的免疫反应。