The first demonstration of virus-like particles expressed from a modified mRNA cocktail
The COVID-19 outbreak in China has been kept under control thanks to tremendous efforts from the government and the people. The rising occurrence of coronaviruses over the past decades, however, seems to indicate that they may become seasonal threats like flu viruses. It is, therefore, imperative to develop such vaccines against coronaviruses, especially COVID-19 at the moment.
A joint research team from Fudan University, Shanghai JiaoTong University, and RNACure Biopharma is currently working on a vaccine for COVID-19. Led by Professor Lin Jinzhong from Fudan University, the research team is developing a messenger RNA (mRNA) vaccine against COVID-19.
mRNAs are biological molecules that all living cells use as blueprints to synthesize proteins. When we are administered with an mRNA vaccine, our body will produce proteins, which are viral antigens, based on the coding information of the mRNAs, The viral antigens will then elicit an immune response to produce protective antibodies.
mRNA Sequence Optimization Pipeline
The scientists are employing two strategies to develop mRNA vaccines against COVID-19. One is to use mRNA to express the receptor-binding domain of the spike protein of COVID-19 to induce neutralizing-antibodies in human body. The other, which the research team has been placing the most emphasis on, is to formulate mRNAs that can instruct the host to produce virus-like particles (VLPs), with morphological and structural features similar to those of native COVID-19 viruses and activate immune responses,
According to the scientists, VLPs are an excellent choice of vaccines, with efficacy comparable to that of live-attenuated viruses. However, live-attenuated viruses have biosafety concerns as they may revert to become infectious again, whereas VLPs offer a much safer option as they contain no genetic material of virus replication.
Although the streamlined manufacturing of mRNA molecules, combined with the superior flexibility in the antigen screening, can greatly accelerate the development process, initial antigen selection and optimization of mRNA sequences are crucial for the efficacy and safety of an mRNA vaccine.
Virus-like particles expressed from the modified mRNA cocktail under an electron microscope
After extensive optimization, the research team formulated an mRNA cocktail containing three genes of COVID-19, which produce VLPs when used to co-transfect human cells.
This is the first time the world has witnessed modified mRNAs that can synthesize VLPs. Observation under an electron microscope reveals the VLPs’ close resemblance to the COVID-19 virus, suggesting it might be a good choice for the vaccine.
Editor: Deng Jianguo, Li Yijie