RESUMO
Although successful COVID-19 vaccines have been developed, multiple pathogenic coronavirus species exist, urging for development of multi-species coronavirus vaccines. Here we developed prototype LNP-mRNA vaccine candidates against SARS-CoV-2 (Delta variant), SARS-CoV and MERS-CoV, and test how multiplexing of these LNP-mRNAs can induce effective immune responses in animal models. A triplex scheme of LNP-mRNA vaccination induced antigen-specific antibody responses against SARS-CoV-2, SARS-CoV and MERS-CoV, with a relatively weaker MERS-CoV response in this setting. Single cell RNA-seq profiled the global systemic immune repertoires and the respective transcriptome signatures of multiplexed vaccinated animals, which revealed a systemic increase in activated B cells, as well as differential gene expression signatures across major adaptive immune cells. Sequential vaccination showed potent antibody responses against all three species, significantly stronger than simultaneous vaccination in mixture. These data demonstrated the feasibility, antibody responses and single cell immune profiles of multi-species coronavirus vaccination. The direct comparison between simultaneous and sequential vaccination offers insights on optimization of vaccination schedules to provide broad and potent antibody immunity against three major pathogenic coronavirus species. One sentence summaryMultiplexed mRNA vaccination in simultaneous and sequential modes provide broad and potent immunity against pathogenic coronavirus species.
RESUMO
This network analysis is to determine the most effective treatment in HBeAg-positive patients. PubMed databases were searched for randomized controlled trials. Bayesian network meta-analysis was used to calculate the pairwise hazard ratios, 95% credible intervals, and ranking of surrogate outcomes. 9 studies were identified. The results show that NA add-on PEG IFN might be a better antiviral approach for HBeAg-positive patients in end point of treatment, with a comparable results of nucleoside/nucleotide analogs (NA), PEG IFN, PEG IFN add-on NA, PEG IFN combined NA, and PEG IFN combined placebo in alanine aminotransferase (ALT) normalization and HBV DNA undetectable. Cumulative probabilities of being the most efficacious treatment were NA add-on PEG IFN (30%) for HBeAg loss. The second efficacious (23%) is HBeAg seroconversion. This network analysis shows that NA add-on PEG IFN might be a better antiviral approach for HBeAg-positive patients in end point of treatment. But the long-term efficiency should be further determined.
