Enhancement of mucosal antibody responses to HIV vaccine

描述（由申请人提供）：自1981年艾滋病毒首次被确认为严重和致命的疾病以来，感染人数已上升至近6000万。每天约有14，000例新的艾滋病毒感染，世卫组织预测，艾滋病毒将在未来几年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，但它仍然是一个基本上没有得到满足的医疗需求。与这种疾病相关的严重性质和不良预后，加上全球高流行率和缺乏简单有效的治疗，推动了对艾滋病毒预防性疫苗的需求。与其他传染病一样，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流行病斗争的首选方法。尽管开发有效的艾滋病毒疫苗仍然是最高优先事项之一，但它也给研究人员带来了巨大的科学挑战。目前没有艾滋病毒疫苗。Zetra Biologicals，LLC独家授权埃默里大学的新平台技术用于疫苗发现、开发和生产。最近的数据，通过使用我们的专利保护和专利申请中的技术，证明了嵌合病毒样颗粒疫苗候选物引起强烈的先天性和获得性免疫应答。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细胞应答。在该项目的第一阶段，我们计划利用我们在创造新型HIV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HIV候选疫苗。我们的目标是创建嵌合VLP与膜锚定的Toll样受体配体作为一种新的HIV-1疫苗候选人的目标，广泛的抗HIV中和抗体和强大的粘膜免疫应答。I期项目的具体目标是：1）生产包含HIV糖蛋白和膜锚定佐剂分子的嵌合病毒样颗粒（cVLP）; 2）与含有Env和Gag蛋白的标准VLP相比，评价新型HIV嵌合VLP的免疫原性。公共卫生相关性：6 000多万人感染了艾滋病毒，艾滋病夺去了2 000多万成人和儿童的生命。每天有14 000名新的艾滋病毒感染者，艾滋病毒继续蔓延。我们最近对HIV-1和SIV的研究表明，使用我们的新型平台技术生产的疫苗可以为开发有效、安全且负担得起的HIV疫苗提供替代策略。在拟议的项目中，我们将证明，新的嵌合病毒样颗粒与纳入toll样受体配体将诱导和增强对HIV-1病毒的免疫反应。

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.