Julio Carrera Montoya, S. Collett, Daniel Fernandez Ruiz, Linda Earnest, M. A. Edeling, A. Yap, C. Y. Wong, James P. Cooney, Kathryn C. Davidson, Jason Roberts, Steven Rockman, B. Tran, Julie L. McAuley, Georgia Deliyannis, S. Grimley, Damian F. J. Purcell, S. Waters, Dale I. Godfrey, Dhiraj Hans, Marc Pellegrini, Jason M. Mackenzie, E. Vincan, William R. Heath, Joseph Torresi
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引用次数: 0
摘要
现有的 mRNA COVID-19 疫苗在减少严重病例和死亡人数方面显示出了功效。然而,这些疫苗对新出现的 SARS-CoV-2 变体引起的感染的有效性已大大减弱,因此有必要开发变体疫苗。理想的情况是,下一代疫苗能够引起更广泛、更持久的免疫反应,以有效对抗新的变种。此外,更接近人类病毒中和的体外试验将大大有助于分析疫苗诱导的保护性抗体反应。在此,我们介绍了一种 SARS-CoV-2 VLP 疫苗的研究结果,该疫苗包含三种关键的结构蛋白:尖峰蛋白(S)、包膜蛋白(E)和膜蛋白(M)。通过替代病毒中和试验确定,VLP 疫苗能有效产生中和抗体,并诱导病毒特异性 T 细胞反应:主要是 CD4+,但也检测到 CD8+ T 细胞反应。与单独使用疫苗相比,使用 AddaVax 的疫苗产生的 T 细胞反应更为明显。佐剂疫苗对小鼠的活病毒挑战具有完全保护作用。此外,我们利用空气-液体-界面(ALI)分化的人鼻上皮细胞(HNE)作为体外系统,该系统可真实模拟人类 SARS-CoV-2 感染和中和。我们的研究表明,接种过 VLP 疫苗的小鼠的免疫血清能完全中和 SARS-CoV-2 病毒感染,这证明 ALI-HNE 有潜力评估疫苗诱导的 Nab。
Human Nasal Epithelium Organoids for Assessing Neutralizing Antibodies to a Protective SARS-CoV-2 Virus-like Particle Vaccine
Existing mRNA COVID-19 vaccines have shown efficacy in reducing severe cases and fatalities. However, their effectiveness against infection caused by emerging SARS-CoV-2 variants has waned considerably, necessitating the development of variant vaccines. Ideally, next-generation vaccines will be capable of eliciting broader and more sustained immune responses to effectively counteract new variants. Additionally, in vitro assays that more closely represent virus neutralization in humans would greatly assist in the analysis of protective vaccine-induced antibody responses. Here, we present findings from a SARS-CoV-2 VLP vaccine encompassing three key structural proteins: Spike (S), Envelope (E), and Membrane (M). The VLP vaccine effectively produced neutralizing antibodies as determined by surrogate virus neutralization test, and induced virus-specific T-cell responses: predominantly CD4+, although CD8+ T cell responses were detected. T cell responses were more prominent with vaccine delivered with AddaVax compared to vaccine alone. The adjuvanted vaccine was completely protective against live virus challenge in mice. Furthermore, we utilized air–liquid-interface (ALI)-differentiated human nasal epithelium (HNE) as an in vitro system, which authentically models human SARS-CoV-2 infection and neutralization. We show that immune sera from VLP-vaccinated mice completely neutralized SARS-CoV-2 virus infection, demonstrating the potential of ALI-HNE to assess vaccine induced Nab.