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

SBIR一期项目旨在开发一种抗癌疫苗。一种成功的癌症疫苗可以通过为患者提供持久的保护和防止复发，而没有通常与化疗和放疗相关的有害副作用，从而可能彻底改变癌症的治疗和预防。抗癌疫苗开发的主要挑战之一是癌症抗原的低免疫原性，特别是肿瘤相关碳水化合物抗原。为了克服这一点，本项目将开发一种基于噬菌体Qbeta的新型载体系统。一种代表性的碳水化合物抗原GD2将与噬菌体qβ连接，这可以引发高滴度的抗体，从而杀死癌细胞。这类疫苗的成功商业化开发将极大地造福于美国乃至全世界的癌症患者。除了癌症疫苗外，基于噬菌体Qbeta的载体是引发强大抗体反应的新平台技术。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平台可以为单克隆抗体的产生提供一个很好的起点，单克隆抗体是治疗和诊断中开发的顶级药物之一。因此，优良载体的可用性可以潜在地解决广泛的生物医学需求。SBIR一期项目旨在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。传统疫苗通常含有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，该领域正在更多地关注明确定义的亚基作为疫苗设计的表位。由于亚基往往具有较低的免疫原性，免疫原性载体对于将所需抗原传递到免疫系统并增强免疫反应至关重要。然而，只有少数携带者在临床研究中得到了验证。由于抗载体抗体的干扰，有限的载体选择会显著降低疫苗的效力。本项目开发了一种基于噬菌体Qbeta的新型免疫原性载体，与金标准载体蛋白相比，它能够激发更高水平的IgG抗体。新的Qbeta突变体将可引起针对目标抗原的高水平IgG抗体。新的Qbeta载体的效用将被证明在传递肿瘤相关的碳水化合物抗原，即神经节苷脂GD2衍生物，以诱导有效的抗癌IgG抗体。如果成功，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。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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.