Tang Justin, Amin Md Al, Campian Jian L
Department of Biomedical Science, University of Guelph, Guelph, ON N1G 2W1, Canada.
Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA.
Vaccines (Basel). 2025 May 15;13(5):524. doi: 10.3390/vaccines13050524.
Over the past several decades, viral vector-based vaccines have emerged as some of the most versatile and potent platforms in modern vaccinology. Their capacity to deliver genetic material encoding target antigens directly into host cells enables strong cellular and humoral immune responses, often superior to what traditional inactivated or subunit vaccines can achieve. This has accelerated their application to a wide array of pathogens and disease targets, from well-established threats like HIV and malaria to emerging infections such as Ebola, Zika, and SARS-CoV-2. The COVID-19 pandemic further highlighted the agility of viral vector platforms, with several adenovirus-based vaccines quickly authorized and deployed on a global scale. Despite these advances, significant challenges remain. One major hurdle is pre-existing immunity against commonly used vector backbones, which can blunt vaccine immunogenicity. Rare but serious adverse events, including vector-associated inflammatory responses and conditions like vaccine-induced immune thrombotic thrombocytopenia (VITT), have raised important safety considerations. Additionally, scaling up manufacturing, ensuring consistency in large-scale production, meeting rigorous regulatory standards, and maintaining equitable global access to these vaccines present profound logistical and ethical dilemmas. In response to these challenges, the field is evolving rapidly. Sophisticated engineering strategies, such as integrase-defective lentiviral vectors, insect-specific flaviviruses, chimeric capsids to evade neutralizing antibodies, and plug-and-play self-amplifying RNA approaches, seek to bolster safety, enhance immunogenicity, circumvent pre-existing immunity, and streamline production. Lessons learned from the COVID-19 pandemic and prior outbreaks are guiding the development of platform-based approaches designed for rapid deployment during future public health emergencies. This review provides an exhaustive, in-depth examination of the historical evolution, immunobiological principles, current platforms, manufacturing complexities, regulatory frameworks, known safety issues, and future directions for viral vector-based vaccines.
在过去几十年中，基于病毒载体的疫苗已成为现代疫苗学中一些最通用、最有效的平台。它们能够将编码靶抗原的遗传物质直接递送至宿主细胞，从而引发强烈的细胞免疫和体液免疫反应，通常优于传统的灭活疫苗或亚单位疫苗所能达到的效果。这加速了它们在多种病原体和疾病靶点上的应用，从如艾滋病毒和疟疾等既定威胁，到如埃博拉病毒、寨卡病毒和严重急性呼吸综合征冠状病毒2（SARS-CoV-2）等新发感染。新冠疫情进一步凸显了病毒载体平台的灵活性，几种基于腺病毒的疫苗迅速获得授权并在全球范围内部署。尽管取得了这些进展，但重大挑战依然存在。一个主要障碍是对常用载体骨架的预先存在的免疫力，这可能会削弱疫苗的免疫原性。罕见但严重的不良事件，包括与载体相关的炎症反应以及如疫苗诱导的免疫性血栓性血小板减少症（VITT）等病症，引发了重要的安全性考量。此外，扩大生产规模、确保大规模生产的一致性、满足严格的监管标准以及维持这些疫苗在全球的公平可及性，都带来了深刻的后勤和伦理困境。为应对这些挑战，该领域正在迅速发展。复杂的工程策略，如整合酶缺陷型慢病毒载体、昆虫特异性黄病毒、用于逃避中和抗体的嵌合衣壳以及即插即用的自我扩增RNA方法，旨在提高安全性、增强免疫原性、规避预先存在的免疫力并简化生产。从新冠疫情和先前疫情中吸取的经验教训正在指导基于平台的方法的开发，这些方法旨在在未来公共卫生紧急情况期间实现快速部署。本综述对基于病毒载体的疫苗的历史演变、免疫生物学原理、当前平台、生产复杂性、监管框架、已知的安全问题以及未来方向进行了详尽、深入的探讨。
