SBIR Phase I: Nanoparticle Enhanced Antibody Production

这个小型企业创新研究第一阶段项目建议证明使用纳米颗粒作为增强抗体生产的佐剂的可行性。市场上有许多佐剂可用于动物体内，以促进抗体的产生，但大多数佐剂都有潜在的危险，如过度的炎症导致慢性肉芽肿的形成、无菌脓肿和/或溃烂组织的坏死。最重要的是，低抗体效价导致抗体产量较低，这增加了使用更多动物来产生抗体的需要。因此，在本项目的第一阶段，我们将研究无镉纳米粒子的结构、表面涂层、大小、表面电荷和抗原密度对动物免疫原性的影响。我们将优化纳米佐剂的配方(共价或电荷纳米颗粒-抗原相互作用)，并研究产生的抗体的生物亲和力。我们预计，建议的纳米佐剂将增加抗原的免疫原性，抗体效价将比没有纳米佐剂的抗体效价高10倍。该项目的更广泛影响/商业潜力依赖于抗体产品，这些产品是增长最快、最活跃和最有前景的药物类别，特别是随着人类免疫疗法的增长。2007年，基于抗体的治疗方法的全球收入约为200亿美元，并以每年14%的速度增长。抗体属于一种安全和靶向特定的药物类别，从早期临床研究到获得许可，这种药物的成功率相对较高。所提出的无机纳米颗粒佐剂可以显著提高抗原的免疫原性并产生高滴度的抗体。该项目的成功开发将大大降低抗体生产成本，有利于人类医疗保健和生物医学研究。此外，它还可以消除疼痛、炎症等对动物的副作用，以及减少使用的动物数量。

This Small Business Innovation Research Phase I project proposes to demonstrate the feasibility of using nanoparticles as an adjuvant for enhanced antibody production. A number of adjuvants are commercially available for use in animals to boost antibody production, but most of them pose potential hazards such as excessive inflammation leading to the formation of chronic granulomas, sterile abscesses, and/or ulcerating tissue necrosis. Most importantly, low antibody titer causes lower yield of antibody, which increases the need to use more animals to produce antibodies. Thus, in Phase I of this project, we will study the effects of cadmium-free nanoparticle structure, surface coating, size, surface charge, and antigen density on animal immunogenicity. We will optimize the formulation of the nanoadjuvant (covalent or charge-charge nanoparticle-antigen interaction) and study the bio-affinity of the antibodies produced. We expect that the proposed nanoadjuvant will increase the immunogenicity of the antigen and that the antibody titer will be 10 times higher than that without the nanoadjuvant.The broader impact/commercial potential of this project relies on antibody products that are the fastest growing, most active, and most promising class of pharmaceuticals, especially with the growth of human immunotherapy. The worldwide revenues of antibody-based therapeutic treatments generated around $20 billion in 2007 and were growing at 14% a year. Antibodies belong to a safe and target-specific category of pharmaceuticals that have a relatively high success rate from early clinical studies to licensure. The proposed inorganic nanoparticle-based adjuvant can dramatically increase the immunogenicity of antigens and produce high antibody titers. Successful development of this project will greatly reduce the cost of antibody production to benefit human healthcare and biomedical research. Furthermore, it can eliminate pain, inflammation and other side effects to animal, as well as reduce the number of animals used.