Single-dose rAAV5-based vaccine provides long-term protective immunity against SARS-CoV-2 and its variants
Brief intro:
- Author: 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
- Journal: Virol J
- Doi: https://www.doi.org/10.1186/s12985-022-01940-w
- Publication Date: 2022 Dec 9
Products/Services used in the paper
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
Abstract
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.
About PackGene
PackGene Biotech is a world-leading CRO and CDMO, excelling in AAV vectors, mRNA, plasmid DNA, and lentiviral vector solutions. Our comprehensive offerings span from vector design and construction to AAV, lentivirus, and mRNA services. With a sharp focus on early-stage drug discovery, preclinical development, and cell and gene therapy trials, we deliver cost-effective, dependable, and scalable production solutions. Leveraging our groundbreaking π-alpha 293 AAV high-yield platform, we amplify AAV production by up to 10-fold, yielding up to 1e+17vg per batch to meet diverse commercial and clinical project needs. Moreover, our tailored mRNA and LNP products and services cater to every stage of drug and vaccine development, from research to GMP production, providing a seamless, end-to-end solution.
