ABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic underlines the urgent need for effective mRNA vaccines. However, current understanding of the immunological outcomes of mRNA vaccines formulated under different nanoplatforms is insufficient. Here, severe acute respiratory syndrome coronavirus 2 receptor binding domain mRNA delivered via lipid nanoparticle (LNP), cationic nanoemulsion (CNE), and cationic liposome (Lipo) was constructed. Results demonstrated that the structural and biochemical characteristics of nanoparticles shaped their tissue dissemination, cellular uptake, and intracellular trafficking, which eventually determined the activation of antiviral humoral and cellular immunity. Specifically, LNP was mainly internalized by myocyte and subsequently circumvented lysosome degradation, giving rise to humoral-biased immune responses. Meanwhile, CNE and Lipo induced cellular-preferred immunity, which was respectively attributed to the better lysosomal escape in dendritic cells and the superior biodistribution in secondary lymphoid organs. Overall, this study may guide the design and clinical use of mRNA vaccines against COVID-19.
Subject(s)
COVID-19 , Nanoparticles , Humans , SARS-CoV-2 , RNA, Messenger/genetics , COVID-19 Vaccines , Tissue Distribution , Immunity, CellularABSTRACT
Messenger RNA (mRNA), which is composed of ribonucleotides that carry genetic information and direct protein synthesis, is transcribed from a strand of DNA as a template. On this basis, mRNA technology can take advantage of the body's own translation system to express proteins with multiple functions for the treatment of various diseases. Due to the advancement of mRNA synthesis and purification, modification and sequence optimization technologies, and the emerging lipid nanomaterials and other delivery systems, mRNA therapeutic regimens are becoming clinically feasible and exhibit significant reliability in mRNA stability, translation efficiency, and controlled immunogenicity. Lipid nanoparticles (LNPs), currently the leading non-viral delivery vehicles, have made many exciting advances in clinical translation as part of the COVID-19 vaccines and therefore have the potential to accelerate the clinical translation of gene drugs. Additionally, due to their small size, biocompatibility, and biodegradability, LNPs can effectively deliver nucleic acids into cells, which is particularly important for the current mRNA regimens. Therefore, the cutting-edge LNP@mRNA regimens hold great promise for cancer vaccines, infectious disease prevention, protein replacement therapy, gene editing, and rare disease treatment. To shed more lights on LNP@mRNA, this paper mainly discusses the rational of choosing LNPs as the non-viral vectors to deliver mRNA, the general rules for mRNA optimization and LNP preparation, and the various parameters affecting the delivery efficiency of LNP@mRNA, and finally summarizes the current research status as well as the current challenges. The latest research progress of LNPs in the treatment of other diseases such as oncological, cardiovascular, and infectious diseases is also given. Finally, the future applications and perspectives for LNP@mRNA are generally introduced.
ABSTRACT
[Objective] Analyze the occurrence of novel coronavirus pneumonia(NCP) in China mainland, explore the epidemiological rules, and evaluate the effect of prevention and control. [Methods] From December 1, 2019 to March 4, 2020, Analysis of 80,409 confirmed cases of NCP in China mainland. [Results] From December 1, 2019 to March 4, 2020, a total of 80,409 cases of NCP were confirmed in China mainland, a total of 67,466 cases were confirmed in Hubei Province, a total of 49,671 cases were confirmed in Wuhan city. From December 1, 2019 to March 4, 2020, a total of 3,012 cases of NCP deaths in China mainland, the mortality was 3.75% (3012/80,409); A total of 52045 cases of cured in China mainland; The turning point of the epidemic have been reached since February 18.2020 in China mainland; The spread index of NCP gradually declined since January 27. 2020, and the extinction index of NCP rose little by little since January 29, 2020. [Conclusion] From December 1, 2019 to March 4, 2020, NCP is under control, and the trend of the epidemic will eventually disappearThe turning point of an epidemic that I've created is a great indicator that can calculate the turning date of an outbreak and provide a basis for scientific prevention.