Major Progress in COVID-19 Vaccination through the use of Nanomaterials Designed for Immunotherapy
具有免疫治疗功能的纳米材料在新型冠状病毒疫苗中的重要进展
André Nel
ABSRACT
New vaccination strategies to accomplish herd immunity and reduce the global mortality associated with COVID-19 are urgently needed. In addition to conventional strategies such as live-attenuated and inactivated viral vaccines or the use of viral-vectored vaccines, major recent progress had been made in the use of next-generation nano-enabled vaccines, including delivery of DNA or RNA templates, viral subunits and peptides by custom-designed lipid nanoparticles or viral-like nanoparticles. I will discuss the design strategies that have gone into the manufacturing of representative vaccine candidates, including the necessity to obtain an optimal 3D confirmation of SARS-CoV-2 spike and RBD proteins or their nucleic acid precursors. These design strategies, including the nucleic acid structure, are key for generating effective viral neutralizing antibodies and T-cell responses. I will elucidate the microfluidics construction of lipid-based nanoparticles, which include ionizable cationic lipids for optimal nucleic acid binding and endosomal release through the formation of hexagonal structures. The efficacy accomplished by representative vaccine candidates will be reviewed in terms of animal and human experimentation, including by making comparisons to previous vaccination studies undertaken with SARS-CoV-1 and MERS antigenic components. I will emphasize the importance of achieving vaccine safety through the correct choice of nanoparticle components, antigens and adjuvants to prevent TH2 skewing of the immune response, which could lead to vaccine-induced lung damage or antibody-mediated infection enhancement. There will also be a discussion of the utility of viral subunits and peptide/epitope-based vaccines and how these can be used in future vaccine design to obtain synergistic T-and B-cell memory responses by lymph node targeting strategies. I will address the importance of durable immune responses as well as the possibility that immunogen-driven mutational effects may impact maintenance of immunity. The foregoing information will be used to elucidate the implication of nano-enabled strategies for future vaccine efforts to other potentially pandemic disease agents as well as cancer immunotherapy. I will elucidate some of this potential by showing a few examples of our own work in the area of cancer immunotherapy and production of a COVID subunit vaccinating nanoparticle.
为了实现获得性免疫及减少新冠病毒带来的全球死亡率，迫切需要开发针对该病毒的新型疫苗。除了减毒活疫苗或使用病毒载体疫苗等常规策略外，在下一代纳米疫苗的使用方面也取得了一系列最新进展，如：设计制备脂质纳米颗粒或病毒样纳米颗粒对DNA、RNA、病毒亚单位和多肽的递送。我将讨论代表性候选疫苗的设计策略，包括获得SARS-CoV-2 spike和RBD蛋白或其核酸前体的最佳3D构象的必要性。这些设计策略，包括核酸结构，是产生有效的病毒中和抗体和T细胞反应的关键。我将阐明基于脂质纳米颗粒的微流控制备，其中包括可电离的阳离子脂质，可通过形成六边形结构实现最佳的核酸结合和内体释放。代表性候选疫苗所实现的功效将通过动物和人类实验来评估，包括与之前对SARS-CoV-1和MERS抗原成分进行的疫苗接种研究进行比较。我将强调通过正确选择纳米颗粒成分，抗原以及佐剂，来防止TH2免疫应答倾斜（这可能导致疫苗引起的肺损伤或抗体介导的感染增强）来实现疫苗安全的重要性。还将讨论病毒亚基和基于多肽/蛋白表位的疫苗的实用性，以及如何将它们用于未来的疫苗设计中，以通过淋巴结靶向策略获得协同的T细胞和B细胞记忆应答。我将讨论持久免疫反应的重要性以及免疫原驱动的突变效应可能影响免疫维持的可能性。上述信息将用于阐明纳米策略对未来疫苗工作对其他潜在大流行性疾病以及癌症免疫疗法的影响。我将通过展示一些我们自己在癌症免疫治疗和制备COVID亚单位疫苗纳米颗粒方面的工作实例来阐明这种潜力。
BIOGRAPHY
Andre Nel is a Distinguished Professor of Medicine at UCLA, where he has established a large federally-funded nanotechnology research program dealing with nanomaterial safety, and nanotherapeutics. The UC Center for the Environmental Implications of Nanotechnology (UC CEIN) is a premier think tank for the safe and sustainable implementation of nanotechnology in the US, while the team-based science efforts he has helped to establish as Research Director of the California Nanosystems Institute have spearheaded nanomedicine translation and commercialization on the UCLA campus. Professor Nel is a recipient of the Harry Truman Award and also received the California Governor’s Environmental Economic Leadership Award on behalf of UC CEIN. He plays a national leadership role in science, biomedical research, nanotechnology and policy. He served as a chair of an internal NIH study section and was a NSF panel member for producing a comprehensive US Government blueprint for nanotechnology development in the US from 2010-2020. He was a member of the US Bilateral Presidential Commission for technology cooperation with Russia, and served as a panel member on Pres. Obama’s PCAST panel for strategizing the NNI technological innovation and commercialization. Dr Nel represented the US State Department and the NIH in cooperative research agreements with the Chinese Academy of Sciences, in which he was recognized as Honorary Foreign Professor. In addition to groundbreaking work in nanotechnology, Dr Nel was Principal Investigator of the NIH-funded UCLA Asthma Center and received the John Salvaggio Award for outstanding service to the American Academy of Asthma Allergy and Immunology. His current nanomedicine research addresses targeting of the immune system by nanoparticles to accomplish chemotherapy and immunotherapy of cancer, as well as the treatment of allergic disorders and autoimmune disease by tolerogenic nanoparticles. He is a frequently invited plenary speaker at international scientific conferences, listed as a Clarivate Analytics highly cited scholar, inventor of multiple patents and founder of two startup companies.
Andre Nel教授是加州大学洛杉矶分校（UCLA）的Distinguished Professor，主要从事纳米材料安全性和纳米医学的研究。Nel教授为UC CEIN（The UC Center for the Environmental Implications of Nanotechnology）研究中心主任，是美国安全和可持续实施纳米技术的智囊团成员之一。Andre Nel教授同时任加利福尼亚纳米系统研究所（California NanoSystems Institute）的Research Director，统领该研究所的纳米科技基础研究、成果转化和产业化。Andre Nel教授是哈里·杜鲁门奖的获得者，并且代表UC CEIN获得了加州州长的环境经济领导奖。他在科学、生物医学研究、纳米技术和政策方面发挥着国家领导作用。他曾担任NIH内部研究部门的主席，并且是NSF小组成员，参与为美国政府制定2010年至2020年纳米技术发展的全面蓝图。作为美国双边总统委员会的成员，Nel教授参与与俄罗斯进行技术合作的讨论，并担任Pres的小组成员。Nel教授还是前总统奥巴马的PCAST小组成员，负责制定NNI技术创新和商业化策略。Andre Nel教授代表美国国务院和美国国立卫生研究院（NIH）与中国科学院签署了合作研究协议，并被评选为中科院名誉外籍教授。除了在纳米技术方面的开创性工作外，Andre Nel教授还是美国国立卫生研究院资助的UCLA哮喘中心的首席研究员，并因对美国哮喘过敏和免疫学学院的杰出贡献而获得约翰·萨尔瓦乔奖。他目前的纳米医学研究致力于通过纳米颗粒靶向治疗，这包括通过设计耐受性纳米颗粒来治疗过敏性疾病和自身免疫性疾病等。Nel教授多次在国际科学会议上受邀担任全会发言人，被列为Clarivate Analytics的高被引学者，多项专利的发明者和两家纳米医药初创公司的创始人。