艾博生物已建立了具有自主知识产权的mRNA和纳米递送技术平台
  • 信使核糖核酸(mRNA)是由DNA模板转录而来,携带遗传信息,指导细胞生产胞内蛋白、膜蛋白及胞外蛋白。
  • 通过修饰碱基和序列优化可提高mRNA的表达水平,调控mRNA的先天免疫激活
  • LNP保护mRNA免于降解,实现高效的体内靶向递送
艾博生物建立了多功能的mRNA药物开发平台
出版物
标题 杂志 摘要
• Monoclonal antibodies represent important weapons in our arsenal to against the COVID-19 pandemic. However, this potential is severely limited by the time-consuming process of developing effective antibodies and the relative high cost of manufacturing. Herein, we present a rapid and cost-effective lipid nanoparticle (LNP) encapsulated-mRNA platform for in vivo delivery of SARS-CoV-2 neutralization antibodies. Two mRNAs encoding the light and heavy chains of a potent SARS-CoV-2 neutralizing antibody HB27, which is currently being evaluated in clinical trials, were encapsulated into clinical grade LNP formulations (named as mRNA-HB27- LNP). In vivo characterization demonstrated that intravenous administration of mRNA-HB27-LNP in mice resulted in a longer circulating half-life compared with the original HB27 antibody in protein format. More importantly, a single prophylactic administration of mRNA-HB27-LNP provided protection against SARS-CoV-2 challenge in mice at 1, 7 and even 63 days post administration. In a close contact transmission model, prophylactic administration of mRNA-HB27-LNP prevented SARS-CoV-2 infection between hamsters in a dose-dependent manner. Overall, our results demonstrate a superior long-term protection against SARS-CoV-2 conferred by a single administration of this unique mRNA antibody, highlighting the potential of this universal platform for antibody-based disease prevention and therapy against COVID-19 as well as a variety of other infectious diseases.
• Briefly, the mRNAs encoding the Omicron RBD were prepared and processed into the final LNP formulation as previously described. The most potent two mRNA constructs, named Omicron/1 and Omicron/2, were selected from a total of 18 mRNAs with different untranslated regions (UTRs) and codon optimizations based on their in vitro expression levels detected by enzyme linked immunosorbent assay (ELISA) .
• After two doses of intramuscularly immunizations at 7-day interval, robust IgG antibodies as well as neutralization antibodies were readily induced by the two ARCoV-Omicrons at 14 days post initial immunization. 
• More importantly, the continuously evolving SARS-CoV-2 calls for the most flexible and deployable mRNA vaccine platform. Starting from the Omicron RBD sequence, it took 32 days to obtain the first set of immunogenicity results from animal studies, and clinical grade vaccine will be ready in less than 3 weeks.
• To our knowledge, this is the first mRNA vaccine candidate against the Omicron variant that has been validated in animals. We are approaching to clinical trials to test the safety and efficacy of ARCoV-Omicron.
• As expected,the majority of fever resolved in the first 2 days after vaccination for all groups.
• The incidence of solicited systemic adverse events was similar after administration of mRNA vaccine as a first or second vaccination.
• Humoral immune responses including anti-RBD IgG and neutralising antibodies increased significantly 7 days after the second dose and peaked between 14 and 28 days thereafter.
• Specific T-cell response peaked between 7 and 14 days after full vaccination.
• 15 μg induced the highest titre of neutralising antibodies, which was about twofold more than the antibody titre of convalescent patients with COVID-19.
• Intramuscular immunization of two doses of mRNA vaccine elicited robust neutralizing antibodies as well as cellular response against SARS-CoV-2 in cynomolgus macaques.
• More importantly, mRNA vaccine vaccination in macaques significantly protected animals from acute lung lesions caused by SARS-CoV-2, and viral replication in lungs and secretion in nasal swabs were completely cleared in all animals immunized with low or high doses of mRNA vaccine.
• No evidence of antibody-dependent enhancement of infection was observed throughout the study.
• Finally, extensive stability assays showed that mRNA vaccine can be stored at 2–8 °C for at least 6 months without decrease of immunogenicity.
• Development of LNP-encapsulated mRNA vaccine targeting the RBD of SARS-CoV-2.
• mRNA vaccine induces neutralizing antibodies and T cell immunity in mice and NHPs.
• Vaccination confers full protection against SARS-CoV-2 challenge in mice.
• A thermostable vaccine candidate for phase I studies.