mRNA vaccine for cancer immunotherapy.

mRNA vaccines have become a promising platform for cancer immunotherapy. During vaccination, naked or vehicle loaded mRNA vaccines efficiently express tumor antigens in antigen-presenting cells (APCs), facilitate APC activation and innate/adaptive immune stimulation. mRNA cancer vaccine precedes other conventional vaccine platforms due to high potency, safe administration, rapid development potentials, and cost-effective manufacturing. However, mRNA vaccine applications have been limited by instability, innate immunogenicity, and inefficient in vivo delivery. Appropriate mRNA structure modifications (i.e., codon optimizations, nucleotide modifications, self-amplifying mRNAs, etc.) and formulation methods (i.e., lipid nanoparticles (LNPs), polymers, peptides, etc.) have been investigated to overcome these issues. Tuning the administration routes and co-delivery of multiple mRNA vaccines with other immunotherapeutic agents (e.g., checkpoint inhibitors) have further boosted the host anti-tumor immunity and increased the likelihood of tumor cell eradication. With the recent U.S. Food and Drug Administration (FDA) approvals of LNP-loaded mRNA vaccines for the prevention of COVID-19 and the promising therapeutic outcomes of mRNA cancer vaccines achieved in several clinical trials against multiple aggressive solid tumors, we envision the rapid advancing of mRNA vaccines for cancer immunotherapy in the near future. This review provides a detailed overview of the recent progress and existing challenges of mRNA cancer vaccines and future considerations of applying mRNA vaccine for cancer immunotherapies.

Transmission patterns of COVID-19 in the mainland of China and the efficacy of different control strategies: a data- and model-driven study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak has seriously endangered the health and lives of Chinese people. In this study, we predicted the COVID-19 epidemic trend and estimated the efficacy of several intervention strategies in the mainland of China. METHODS: According to the COVID-19 epidemic status, we constructed a compartmental model. Based on reported data from the National Health Commission of People's Republic of China during January 10-February 17, 2020, we estimated the model parameters. We then predicted the epidemic trend and transmission risk of COVID-19. Using a sensitivity analysis method, we estimated the efficacy of several intervention strategies. RESULTS: The cumulative number of confirmed cases in the mainland of China will be 86 763 (95% CI: 86 067-87 460) on May 2, 2020. Up until March 15, 2020, the case fatality rate increased to 6.42% (95% CI: 6.16-6.68%). On February 23, 2020, the existing confirmed cases reached its peak, with 60 890 cases (95% CI: 60 350-61 431). On January 23, 2020, the effective reproduction number was 2.620 (95% CI: 2.567-2.676) and had dropped below 1.0 since February 5, 2020. Due to governmental intervention, the total number of confirmed cases was reduced by 99.85% on May 2, 2020. Had the isolation been relaxed from February 24, 2020, there might have been a second peak of infection. However, relaxing the isolation after March 16, 2020 greatly reduced the number of existing confirmed cases and deaths. The total number of confirmed cases and deaths would increase by 8.72 and 9.44%, respectively, due to a 1-day delayed diagnosis in non-isolated infected patients. Moreover, if the coverage of close contact tracing was increased to 100%, the cumulative number of confirmed cases would be decreased by 88.26% on May 2, 2020. CONCLUSIONS: The quarantine measures adopted by the Chinese government since January 23, 2020 were necessary and effective. Postponing the relaxation of isolation, early diagnosis, patient isolation, broad close-contact tracing, and strict monitoring of infected persons could effectively control the COVID-19 epidemic. April 1, 2020 would be a reasonable date to lift quarantine in Hubei and Wuhan.