Laboratory of Virology, Wageningen University, Wageningen, The Netherlands.
Bioprocess Engineering, Wageningen University, Wageningen, The Netherlands.
mBio. 2021 Oct 26;12(5):e0181321. doi: 10.1128/mBio.01813-21. Epub 2021 Oct 12.
Vaccines pave the way out of the SARS-CoV-2 pandemic. Besides mRNA and adenoviral vector vaccines, effective protein-based vaccines are needed for immunization against current and emerging variants. We have developed a virus-like particle (VLP)-based vaccine using the baculovirus-insect cell expression system, a robust production platform known for its scalability, low cost, and safety. Baculoviruses were constructed encoding SARS-CoV-2 spike proteins: full-length S, stabilized secreted S, or the S1 domain. Since subunit S only partially protected mice from SARS-CoV-2 challenge, we produced S1 for conjugation to bacteriophage AP205 VLP nanoparticles using tag/catcher technology. The S1 yield in an insect-cell bioreactor was ∼11 mg/liter, and authentic protein folding, efficient glycosylation, partial trimerization, and ACE2 receptor binding was confirmed. Prime-boost immunization of mice with 0.5 μg S1-VLPs showed potent neutralizing antibody responses against Wuhan and UK/B.1.1.7 SARS-CoV-2 variants. This two-component nanoparticle vaccine can now be further developed to help alleviate the burden of COVID-19. Vaccination is essential to reduce disease severity and limit the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Protein-based vaccines are useful to vaccinate the world population and to boost immunity against emerging variants. Their safety profiles, production costs, and vaccine storage temperatures are advantageous compared to mRNA and adenovirus vector vaccines. Here, we use the versatile and scalable baculovirus expression vector system to generate a two-component nanoparticle vaccine to induce potent neutralizing antibody responses against SARS-CoV-2 variants. These nanoparticle vaccines can be quickly adapted as boosters by simply updating the antigen component.
疫苗为走出 SARS-CoV-2 大流行铺平了道路。除了 mRNA 和腺病毒载体疫苗外,还需要有效的基于蛋白质的疫苗来针对当前和新出现的变体进行免疫接种。我们使用杆状病毒-昆虫细胞表达系统开发了一种基于病毒样颗粒(VLP)的疫苗,该系统是一种强大的生产平台,以其可扩展性、低成本和安全性而闻名。杆状病毒被构建为编码 SARS-CoV-2 刺突蛋白:全长 S、稳定分泌的 S 或 S1 结构域。由于亚单位 S 仅部分保护小鼠免受 SARS-CoV-2 攻击,我们使用标签/捕获器技术生产了用于与噬菌体 AP205 VLP 纳米颗粒缀合的 S1。在昆虫细胞生物反应器中,S1 的产量约为 11mg/L,并证实了其正确的蛋白质折叠、有效的糖基化、部分三聚化和 ACE2 受体结合。用 0.5μg S1-VLPs 对小鼠进行的初免-加强免疫显示出针对武汉株和 UK/B.1.1.7 SARS-CoV-2 变体的强大中和抗体反应。这种两价纳米颗粒疫苗现在可以进一步开发,以帮助减轻 COVID-19 的负担。接种疫苗对于减轻疾病严重程度和限制严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)的传播至关重要。基于蛋白质的疫苗可用于为世界人口接种疫苗,并增强对新出现变体的免疫力。与 mRNA 和腺病毒载体疫苗相比,它们的安全性、生产成本和疫苗储存温度具有优势。在这里,我们使用多功能且可扩展的杆状病毒表达载体系统来产生两价纳米颗粒疫苗,以诱导针对 SARS-CoV-2 变体的强大中和抗体反应。这些纳米颗粒疫苗可以通过简单地更新抗原成分快速适应作为加强剂。
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