SBIR Phase I: Development of Bacteriophage Qbeta and Mutants as Carriers for Next Generation Vaccines

这个SBIR第一阶段项目旨在开发一种抗癌疫苗。一种成功的癌症疫苗可能会给癌症的治疗和预防带来革命性的变化，为患者提供持久的保护，防止复发，而不会出现通常与化疗和放射治疗相关的有害副作用。抗癌疫苗开发的主要挑战之一是肿瘤抗原，特别是肿瘤相关糖类抗原的免疫原性低。为了克服这一点，在本项目中，将开发一种基于噬菌体Qbeta的新型载体系统。具有代表性的碳水化合物抗原GD2将与噬菌体Qbeta相连，后者可以诱导出能够杀死癌细胞的高滴度抗体。这种疫苗的成功商业开发不仅将使美国的癌症患者受益，也将使世界各地的癌症患者受益。除了癌症疫苗，基于噬菌体Qbeta的载体是一种新的平台技术，可以诱导强大的抗体反应。对疫苗开发感兴趣的生物技术公司可以将Qbeta作为载体，针对传染病和慢性病。此外，Qbeta平台可以为产生单抗提供一个很好的起点，单抗是用于治疗学和诊断学的顶级试剂之一。因此，优质载体的可用性可能满足广泛的生物医学需求。这项SBIR第一阶段项目建议为下一代疫苗设计新的基于噬菌体Qbeta的载体。疫苗对公众健康产生了巨大的影响。传统疫苗通常将减毒或灭活的细菌或病毒作为免疫原。随着对安全性要求的提高，该领域正更多地关注定义明确的亚基作为疫苗设计的表位。由于亚单位往往具有较低的免疫原性，免疫原性载体对于将所需的抗原传递到免疫系统和增强免疫反应至关重要。然而，只有少数几个可用的载体已经在临床研究中得到验证。由于抗携带者抗体的干扰，有限的携带者选择可能会显著降低疫苗效力。该项目开发了一种基于噬菌体Qbeta的新型免疫原性载体，与黄金标准载体蛋白相比，能够诱导针对目标抗原的更高水平的免疫球蛋白抗体。新的Qbeta突变体将可用来诱导针对目标抗原的高水平抗体。新的Qbeta载体在运送肿瘤相关碳水化合物抗原，即神经节苷脂GD2衍生物方面的效用将被证明，以诱导有效的抗癌IgG抗体。一旦成功，基于GD2的疫苗将是该领域的一个巨大飞跃，因为它将是有史以来第一个基于碳水化合物的抗癌疫苗。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

This SBIR Phase I project aims to develop an anti-cancer vaccine. A successful vaccine against cancer can potentially revolutionize cancer treatment and prevention by providing durable protection to patients and preventing relapse, without the harmful side effects commonly associated with chemo- and radiation- therapies. One of the major challenges in anti-cancer vaccine development is the low immunogenicity of cancer antigens, in particular tumor associated carbohydrate antigens. In order to overcome this, in this project, a new carrier system based on bacteriophage Qbeta will be developed. A representative carbohydrate antigen GD2 will be linked with bacteriophage Qbeta, which can elicit superior titers of antibodies that can kill cancer cells. Successful commercial development of such vaccines will greatly benefit cancer patients not only in the US, but also throughout the world. In addition to cancer vaccines, the bacteriophage Qbeta based carrier is a new platform technology to elicit powerful antibody responses. Biotechnological companies interested in vaccine development can adapt Qbeta as the carrier to target infectious diseases and chronic diseases. Furthermore, the Qbeta platform can provide an excellent starting point for the generation of monoclonal antibodies, which are among the top agents developed for therapeutics and diagnostics. Thus, the availability of a superior carrier can potentially address a wide range of biomedical needs.This SBIR Phase I project proposes to design new bacteriophage Qbeta based carriers for next generation vaccines. Vaccines have had tremendous impacts on public health. Traditional vaccines commonly incorporate attenuated or killed bacteria or viruses as immunogens. With the enhanced requirements on safety, the field is focusing more on well-defined subunits as epitopes for vaccine design. As subunits tend to have lower immunogenicity, immunogenic carriers are critical to deliver the desired antigen to the immune system and to enhance the immune responses. However, there are only a few carriers available that have been validated in clinical studies. The limited choices of carriers can significantly reduce vaccine efficacy due to interferences from anti- carrier antibodies. This project develops a new class of immunogenic carrier based on bacteriophage Qbeta capable of eliciting superior levels of IgG antibodies to the target antigen compared to gold standard carrier proteins. Novel mutants of Qbeta will become available to elicit high levels of IgG antibodies against the target antigen. The utility of the new Qbeta carrier will be demonstrated in delivering a tumor associated carbohydrate antigen, i.e., ganglioside GD2 derivative, to induce potent anti-cancer IgG antibodies. When successful, the GD2 based vaccine will be a quantum leap for the field as it will be the first ever carbohydrate based anticancer vaccine.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.