Display of HIV-1 Epitopes on Plant Virus Particles

描述(申请人提供)：人类免疫缺陷病毒1型(HIV-1)大流行现在对人类发病率和死亡率以及全球经济的影响超过了所有其他已知的流行病。迫切需要一种有效且具有成本效益的疫苗，但事实证明，这是一项巨大的科学挑战。理想情况下，HIV-1疫苗将诱导对感染多种病毒变种的无菌免疫。疫苗组合的开发取得了一些显着的进展，能够在非人类灵长类动物模型中产生针对艾滋病发展的显着水平的保护。这些疫苗允许动物通过强大的病毒特异性细胞毒性T细胞的启动来控制病毒的挑战，但这不能防止感染，诱导中和抗体的机制仍然是一个重要的目标。重组病毒样颗粒在开发能够诱导高水平抗体产生的有效免疫原方面显示出巨大的希望。大型生物公司开发了一种基于杆状植物病毒的病毒样颗粒抗原展示系统。代表HIV-1中和抗体结合部位的线性表位和HIV-1表面糖蛋白环结构将在杆状烟草花叶病毒和痘病毒表面以有序、重复、准晶的方式展示，并有望诱导高水平的多肽特异性抗体。将采用多种方法加强HIV-1重组病毒的表达和纯化。重组病毒将通过生物物理、化学和免疫学方法进行表征。看似有希望的重组病毒将用于免疫豚鼠，豚鼠血清将用于体外检测HIV-1的中和活性。中和活性的展示将证明未来开发用于HIV-1亚单位疫苗的植物病毒多肽展示系统的工作是合理的。该系统非常容易扩大规模，并允许生产极其廉价、有效的疫苗。

DESCRIPTION (provided by applicant): The human immunodeficiency virus type 1 (HIV-1) pandemic now eclipses all other known epidemics in terms of its impact on human morbidity and mortality, as well as the global economy. The need for an efficacous and cost effective vaccine is urgent, but has proven to be an enormous scientific challenge. Ideally, an HIV-1 vaccine will induce sterilizing immunity against infection with a broad range of virus variants. There have been some notable advances in development of vaccine regiments that are able to generate significant levels of protection against development of AIDS in non-human primate models. These vaccines allow animals to control viral challenge by strong priming of virus-specific cytotoxic T cells, but this cannot prevent infection and mechanisms to induce neutralizing antibodies remains a vital goal. Recombinant virus-like particles show great promise for development of potent immunogens that are able to induce high levels of antibody production. Large Scale Biology Corporation has developed a virus-like particle antigen display system based on rod-shaped plant viruses. Linear epitopes that represent the binding site of HIV-1 neutralizing antibodies, and HIV-1 surface glycoprotein loop structures will be displayed in ordered, repetitive, quasicrystalline arrays on the surface of rod-shaped tobacco mosaic virus and potexviruses, and are expected to induce high levels of peptide-specific antibodies. Methods to enhance the expression and purification of recombinant viruses displaying HIV-1 peptides will be employed. The recombinant viruses will be characterized by biophysical, chemical and immunological methods. Recombinant viruses that appear promising will be used to immunize guinea pigs, and guinea pig sera will be used to assay for HIV-1 neutralizing activity in vitro. Demonstration of neutralizing activity will justify future work on development of plant virus peptide display systems for HIV-1 subunit vaccines. This system is very easy to scale up, and allows production of extremely cheap, effective vaccines.