Chentoufi Aziz A, Ulmer Jeffrey B, BenMohamed Lbachir
Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, School of Medicine, University of California Irvine, Irvine, CA 92697, USA.
Department of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, CA 92660, USA.
Vaccines (Basel). 2024 Dec 31;13(1):30. doi: 10.3390/vaccines13010030.
The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is in its sixth year and is being maintained by the inability of current spike-alone-based COVID-19 vaccines to prevent transmission leading to the continuous emergence of variants and sub-variants of concern (VOCs). This underscores the critical need for next-generation broad-spectrum pan-Coronavirus vaccines (pan-CoV vaccine) to break this cycle and end the pandemic. The development of a pan-CoV vaccine offering protection against a wide array of VOCs requires two key elements: (1) identifying protective antigens that are highly conserved between passed, current, and future VOCs; and (2) developing a safe and efficient antigen delivery system for induction of broad-based and long-lasting B- and T-cell immunity. This review will (1) present the current state of antigen delivery platforms involving a multifaceted approach, including bioinformatics, molecular and structural biology, immunology, and advanced computational methods; (2) discuss the challenges facing the development of safe and effective antigen delivery platforms; and (3) highlight the potential of nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNP) as the platform that is well suited to the needs of a next-generation pan-CoV vaccine, such as the ability to induce broad-based immunity and amenable to large-scale manufacturing to safely provide durable protective immunity against current and future Coronavirus threats.
由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的新冠疫情已进入第六个年头，由于目前仅基于刺突蛋白的新冠疫苗无法预防传播，导致令人担忧的变异株和亚变异株不断出现，疫情得以持续。这凸显了开发下一代广谱全冠状病毒疫苗（全冠状病毒疫苗）以打破这一循环并结束疫情的迫切需求。开发一种能针对多种令人担忧的变异株提供保护的全冠状病毒疫苗需要两个关键要素：（1）识别在过去、当前和未来令人担忧的变异株之间高度保守的保护性抗原；（2）开发一种安全有效的抗原递送系统，以诱导广泛而持久的B细胞和T细胞免疫。本综述将：（1）介绍抗原递送平台的现状，包括多方面的方法，如生物信息学、分子和结构生物学、免疫学以及先进的计算方法；（2）讨论开发安全有效的抗原递送平台所面临的挑战；（3）强调脂质纳米颗粒（LNP）包裹的核苷修饰mRNA作为一种平台的潜力，该平台非常适合下一代全冠状病毒疫苗的需求，例如能够诱导广泛免疫，并且适合大规模生产，以安全地提供针对当前和未来冠状病毒威胁的持久保护性免疫。
