生物
病毒学
抗体
信使核糖核酸
中和抗体
病毒
Spike(软件开发)
严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)
2019年冠状病毒病(COVID-19)
基因
免疫学
遗传学
医学
疾病
管理
病理
经济
传染病(医学专业)
作者
Magnus A.G. Hoffmann,Zhi Yong Yang,Kathryn E. Huey-Tubman,Alexander A. Cohen,Priyanthi N. P. Gnanapragasam,Leesa M. Nakatomi,Kaya N Storm,Woohyun J. Moon,Paulo J.C. Lin,Anthony P. West,Pamela J. Björkman
出处
期刊:Cell
[Elsevier]
日期:2023-05-01
卷期号:186 (11): 2380-2391.e9
被引量:3
标识
DOI:10.1016/j.cell.2023.04.024
摘要
Prime-boost regimens for COVID-19 vaccines elicit poor antibody responses against Omicron-based variants and employ frequent boosters to maintain antibody levels. We present a natural infection-mimicking technology that combines features of mRNA- and protein nanoparticle-based vaccines through encoding self-assembling enveloped virus-like particles (eVLPs). eVLP assembly is achieved by inserting an ESCRT- and ALIX-binding region (EABR) into the SARS-CoV-2 spike cytoplasmic tail, which recruits ESCRT proteins to induce eVLP budding from cells. Purified spike-EABR eVLPs presented densely arrayed spikes and elicited potent antibody responses in mice. Two immunizations with mRNA-LNP encoding spike-EABR elicited potent CD8+ T cell responses and superior neutralizing antibody responses against original and variant SARS-CoV-2 compared with conventional spike-encoding mRNA-LNP and purified spike-EABR eVLPs, improving neutralizing titers >10-fold against Omicron-based variants for 3 months post-boost. Thus, EABR technology enhances potency and breadth of vaccine-induced responses through antigen presentation on cell surfaces and eVLPs, enabling longer-lasting protection against SARS-CoV-2 and other viruses.
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