Single-dose rAAV5-based vaccine provides long-term protective immunity against SARS-CoV-2 and its variants
简介:
- 作者: Guochao Liao, Hungyan Lau, Zhongqiu Liu, Chinyu Li, Zeping Xu, Xiaoxiao Qi, Yu Zhang, Qian Feng, Runze Li, Xinyu Deng, Yebo Li, Qing Zhu, Sisi Zhu, Hua Zhou, Hudan Pan, Xingxing Fan, Yongchao Li, Dan Li, Liqing Chen, Bixia Ke, Zhe Cong, Qi Lv, Jiangning Liu, Dan Liang, Anan Li, Wenshan Hong, Linlin Bao, Feng Zhou, Hongbin Gao, Shi Liang, Bihong Huang, Miaoli Wu, Chuan Qin, Changwen Ke and Liang Liu
- 杂志: Virol J
- Doi: https://www.doi.org/10.1186/s12985-022-01940-w
- 出版日期: 2022 Dec 9
论文中使用的产品/服务
Quotation shows PackGene:The recombinant type 5 adenoviral-vectored SARSCoV- 2 (Accession Number: MN985325.1) vaccines encoding RBD domain (residues 319-541), RBD-plus domain (residues 319-583), S1 protein (residues 14-685), full-length of S protein (residues 14-1213) and NTD domain (residues 14-305 of the S protein N-terminal domain) of SARS-CoV-2 were produced by PackGene Biotech (Guangzhou, China). Briefly, rAAV5 packaging plasmids were transfected into HEK293T cells using PEI transfection reagent, according to the manufacturer’s protocol. The transfected cells and supernatants were harvested 72 h post transfection. rAAV5- vaccine was purified and titrated by real-time quantitative PCR. rAAV5-vaccine was adjusted to 10^12 GCs/mL in PBS and used for the following vaccinations.
Research Field:Covid-related
Animal or cell line strain:Six weeks-old, 36 weeks-old female BALB/c mice and 6–8 weeks female Wistar rats
摘要
The COVID-19 pandemic, caused by the SARS-CoV-2 virus and its variants, has posed unprecedented challenges worldwide. Existing vaccines have limited effectiveness against SARS-CoV-2 variants. Therefore, novel vaccines to match mutated viral lineages by providing long-term protective immunity are urgently needed. We designed a recombinant adeno-associated virus 5 (rAAV5)-based vaccine (rAAV-COVID-19) by using the SARS-CoV-2 spike protein receptor binding domain (RBD-plus) sequence with both single-stranded (ssAAV5) and self-complementary (scAAV5) delivery vectors and found that it provides excellent protection from SARS-CoV-2 infection. A single-dose vaccination in mice induced a robust immune response; induced neutralizing antibody (NA) titers were maintained at a peak level of over 1:1024 more than a year post-injection and were accompanied by functional T-cell responses. Importantly, both ssAAV- and scAAV-based RBD-plus vaccines produced high levels of serum NAs against the circulating SARS-CoV-2 variants, including Alpha, Beta, Gamma and Delta. A SARS-CoV-2 virus challenge showed that the ssAAV5-RBD-plus vaccine protected both young and old mice from SARS-CoV-2 infection in the upper and lower respiratory tracts. Whole genome sequencing demonstrated that AAV vector DNA sequences were not found in the genomes of vaccinated mice one year after vaccination, demonstrating vaccine safety. These results suggest that the rAAV5-based vaccine is safe and effective against SARS-CoV-2 and several variants as it provides long-term protective immunity. This novel vaccine has a significant potential for development into a human prophylactic vaccination to help end the global pandemic.
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作为一家专注于AAV 技术十余年，深耕基因治疗领域的CRO&CDMO，派真生物可提供从载体设计、构建到 AAV、慢病毒和 mRNA 服务的一站式解决方案。凭借深厚的技术实力、卓越的运营管理和高标准的服务交付，我们为全球客户提供一站式CMC解决方案，包括从早期概念验证、成药性评估到IIT、IND及BLA的各个阶段。
凭借我们独立知识产权的π-alphaTM 293 细胞AAV高产技术平台，我们能将AAV产量提高多至10倍，每批次产量可达1×10¹⁷vg，以满足多样化的商业化和临床项目需求。此外，我们定制化的mRNA和脂质纳米颗粒（LNP）产品及服务覆盖药物和疫苗开发的各个阶段，从研发到符合GMP的生产，提供端到端的一站式解决方案。
