Lyophilized mRNA-lipid nanoparticle vaccines with long-term stability and high antigenicity against SARS-CoV-2.

Advanced mRNA vaccines play vital roles against SARS-CoV-2. However, most current mRNA delivery platforms need to be stored at -20 °C or -70 °C due to their poor stability, which severely restricts their availability. Herein, we develop a lyophilization technique to prepare SARS-CoV-2 mRNA-lipid nanoparticle vaccines with long-term thermostability. The physiochemical properties and bioactivities of lyophilized vaccines showed no change at 25 °C over 6 months, and the lyophilized SARS-CoV-2 mRNA vaccines could elicit potent humoral and cellular immunity whether in mice, rabbits, or rhesus macaques. Furthermore, in the human trial, administration of lyophilized Omicron mRNA vaccine as a booster shot also engendered strong immunity without severe adverse events, where the titers of neutralizing antibodies against Omicron BA.1/BA.2/BA.4 were increased by at least 253-fold after a booster shot following two doses of the commercial inactivated vaccine, CoronaVac. This lyophilization platform overcomes the instability of mRNA vaccines without affecting their bioactivity and significantly improves their accessibility, particularly in remote regions.

Bioinformatics analysis of differentially expressed genes on alopecia.

The molecular mechanism of alopecia areata (AA) is still elusive and here we utilized bioinformatics methods to analyze AA-related differentially expressed genes. In this study, GSE45512 and GSE45513 were downloaded from the NCBI sub-database Gene Expression Omnibus (GEO). The gene expressions of AA and normal samples were analyzed using the R package limma, which showed significant differences between AA and normal samples in two species. These genes were subject to functional annotation and protein interaction networks. At the same time, gene set enrichment analysis was conducted for all differentially expressed genes. The study revealed that a total of 225 differentially expressed genes were screened from human AA samples, and a total of 337 differentially expressed genes were screened from spontaneous AA skin samples in C3H/HeJ mice. There are 23 differentially expressed genes in the two species. GO and protein interaction network analysis shown gene enrichment in immune-related functions, and these proteins interact with each other. Gene set enrichment analysis showed that differential genes from both species were significantly enriched to chemokine signaling pathways, cytokine-cytokine receptor interactions, staphylococcus aureus infection, and antigen processing and presentation. Moreover, the human down-regulated differential gene not only maps to the alopecia in human phenotype ontology, but also maps to the pathologically relevant phenotype of the skin appendage. In brief, 23 significant differentially expressed genes were screened out coexisting in AA human and mouse by bioinformatics methods. In addition, the result demonstrated that AA is closely related to the immune process and skin appendage lesions. These results provide new ideas for the diagnosis and treatment of AA.