Towards an effective mRNA vaccine against 2019-nCoV: demonstration of virus-like particles expressed from a modified mRNA cocktail

摘要: Frequent outbreaks of coronavirus make the development of an effective vaccine imperative. Recently, vaccines based on in-vitro transcribed messenger RNA (mRNA) have shown great potential. The streamlined manufacturing of mRNA molecules, combined with the superior flexibility in the antigen screening, greatly accelerates the development process. When using an mRNA platform to develop a vaccine, initial antigen choice plays a crucial role in determining the final efficacy and safety of the vaccine. Furthermore, mRNA sequences that encode antigens require extensive optimization to ensure highly efficient and sustained expression. Our ongoing efforts to develop an effective mRNA vaccine against 2019-nCoV place emphasis on the virus-like particles (VLPs) as the presenting antigen. At the same time, our second fast track uses mRNA to express the receptor-binding domain of the spike protein(S-RBD). After extensive optimization, an mRNA cocktail containing three genes is able to produce 2019-nCoV virus-like particles highly similar to the native 2019-nCoV. Meanwhile, an mRNA vaccine candidate expressing S-RBD is being tested in mice for its immunogenicity. We will next compare both the efficacy and the safety of the two mRNA vaccines based on S-RBD and VLPs, respectively.