摘要：流行性感冒病毒是公共衛生的重大議題，全球每年至少有300 萬名重症病例，造成約50 萬人死亡。雖然每年有150 億美元挹注於流感疫苗的市場，但現今所採用之傳統疫苗科技需要每年重新製備疫苗與施打，因此，若能利用奈米技術增強流感疫苗效性，將具有極大市場競爭力。奈米科技於疫苗應用有多項優勢，然而，目前仍缺乏有效率的方式將佐劑與奈米粒子作結合。為此，申請者致力於發展一種生物相容性的中空奈米粒子，以雙重乳化法(double emulsion)將佐劑裝載於奈米粒子的中心，並將奈米粒子之表面與重組之病毒抗原連結，成為一個仿生病毒奈米粒子，以達到最佳化之免疫反應。此技術平台預計由奈米科技、重組蛋白質工程、病毒疫苗共三方面之跨院校、跨領域的學者共同建立，將致力於設計、分析與最佳化新型之奈米流感疫苗。初期原型疫苗的組成將包括真核系統表現之血球凝集素(HA)蛋白，與裝載了STING agonist 為佐劑的中空奈米粒子，此奈米疫苗將以小鼠與貂的動物模式評估其安全性及保護效果，除此之外，我們將採用可擴大量產的方式來表現重組蛋白，符合未來商品化製程的目標，並修飾HA 抗原使其能誘發廣泛性中和抗體之免疫反應，同時仍能穩定地與奈米粒子表面連結。預計此技術將獲得多項專利，造就新興就業機會。
Abstract: There is an ongoing effort in developing advanced vaccine formulations against influenza viruses, which cause contagious respiratory illness and pose a significant threat to the public health. Every year, approximately 3-5 million cases of severe illness emerge with 250,000 to 500,000 deaths worldwide, incurring significant economical burden. Expenditures on influenza vaccines amount to 12-15 billion dollars annually, yet the existing vaccine technology is dated and requires annual refreshing to match the circulating viral strain. The disease’s serious and widespread nature presents a compelling opportunity for novel technology development, particularly in vaccine nanotechnology. The application of synthetic nanoparticles has demonstrated significant value in vaccine development. Owing to their physical semblance to viruses in terms of size and morphology, nanoparticle-based vaccines have shown several benefits over traditional subunit vaccines. The advantage of associating antigens and immunological adjuvants in a nanoparticulates for immune stimulation has prompted nanomaterial scientists globally to engineer novel synthetic vaccines to tackle persistent as well as emerging infectious threats. However, despite ongoing efforts, efficient encapsulation of immunological adjuvants in nanoscale particulates remains a major technical challenge. To this end, a proprietary hollow nanoparticle platform consisting of biodegradable and biocompatible materials has been developed in the principal investigator’s laboratory to facilitate facile incorporation of immunological adjuvants. Prepared from a double emulsion method, the nanoparticles enable non-covalent encapsulation of adjuvants without compromising their structure-specific adjuvanting effects. The functionalizable polymeric particle surface also allows for facile association of viral antigens for immune stimulation. It is envisioned that upon administration, the structurally stable, virus-like hollow nanoparticles will promote co-delivery of viral antigen and adjuvants to the immune system, triggering antigen processing in association with precisely tuned danger signals. The technology is expected to introduce a powerful and modular platform for preparing safe and potent vaccine formulations. In light of the significant business opportunity in anti-influenza vaccine development and the advantage of the hollow nanoparticle platform, a team of investigators with combined expertise in nanotechnology, recombinant protein engineering, and vaccinology has been formed to design, characterize, and optimize a novel influenza vaccine. An initial prototype will be constructed using full-length recombinant hemagglutinin (HA) protein and hollow nanoparticles loaded with a STING agonist. The platform will be thoroughly characterized in mice and ferrets to strike an optimal balance between safety and efficacy. In addition, antigen modulation and platform manufacturability will be examined in this study. On one hand, scalable preparation techniques will be employed to obtain the needed parameters toward future product manufacturing; on the other, novel recombinant viral antigens will be engineered with the aim of promoting broadly neutralizing immunity against influenza virus infection and enhancing antigen-nanoparticle association. Completion of the project is expected to generate multiple patents spanning nanotechnology, manufacturing, vaccine formulations, and recombinant protein technology. A cross-disciplinary venture can also be envisioned, offering employment opportunities across engineering, biology, and medical sciences and capitalizing on the advancement of bionanotechnology to address the most serious global health threats.
