Project description:The ongoing COVID-19 pandemic and its unprecedented global societal and economic disruptive impact highlight the urgent need for safe and effective vaccines. Taking substantial advantages of versatility and rapid development, two mRNA vaccines against COVID-19 have completed late-stage clinical assessment at an unprecedented speed and reported positive results. In this review, we outline keynotes in mRNA vaccine development, discuss recently published data on COVID-19 mRNA vaccine candidates, focusing on those in clinical trials and analyze future potential challenges.
Project description:The advent of mRNA vaccines represents a significant advance in the field of vaccinology. While several vaccine approaches (mRNA, DNA, recombinant protein, and viral-vectored vaccines) had been investigated at the start of the COVID-19 pandemic, mRNA vaccines quickly gained popularity due to superior immunogenicity at a low dose, strong safety/tolerability profiles, and the possibility of rapid vaccine mass manufacturing and deployment to rural regions. In addition to inducing protective neutralizing antibody responses, mRNA vaccines can also elicit high-magnitude cytotoxic T-cell responses comparable to natural viral infections; thereby, drawing significant interest from cancer immunotherapy experts. This mini-review will highlight key developmental milestones and lessons we have learned from mRNA vaccines during the COVID-19 pandemic, with a specific emphasis on clinical trial data gathered so far for mRNA vaccines against melanoma and other forms of cancer.
Project description:The current situation of Coronavirus Disease 2019 (COVID-19) worldwide is still very severe. Presently, many breakthroughs have been accomplished in the research and development of drugs for the treatment of COVID-19, especially vaccines; however, some of the so-called COVID-19-specific drugs highlighted in the early stage failed to achieve the expected curative effect. There is no antiviral therapy available, by stimulating protective immunity vaccine is the best choice for the future management of infection. Therefore, we aimed to identify the latest developments in the research and development of these drugs and vaccines and provide a reference for the prevention and treatment of COVID-19.
Project description:Given the interest in the COVID mRNA vaccines, we sought to investigate how the RNA modification N1-methylpseudouridine (and its related modification, pseudouridine) is read by ribosomes and reverse transcriptases. By looking at reverse transcriptase data, we can gain information on how the modification affects duplex stability, which may have important consequences for the tRNA-mRNA interactions found in the ribosome.
Project description:The COVID mRNA vaccines utilize the modified nucleobase N1-methylpseudouridine, in place of canonical uridine, to improve immunogenicity and protein yield. However, relatively few studies have investigated the effect of modified nucleobases on the fidelity of protein translation. Given the interest in the COVID mRNA vaccines, we sought to investigate how N1-methylpseudouridine (and the related modification pseudouridine) is read by ribosomes.
Project description:The search for effective vaccines to stop the COVID-19 pandemic has led to an unprecedented amount of global scientific production and activity. This study aimed to analyze global scientific production on the different vaccine types (mRNA and conventional) that were validated for COVID-19 during the years 2020-2021. The scientific production generated on COVID-19 vaccines during the period 2020-2021 totaled the enormous amount of 20,459 studies published. New mRNA vaccines clearly showed higher production levels than conventional vaccines (viral and inactivated vectors), with 786 and 350 studies, respectively. The USA is the undisputed leader in the global production on COVID-19 vaccines, with Israel and Italy also playing an important role. Among the journals publishing works in this field, the New England Journal of Medicine, the British Medical Journal, and Vaccines stand out from the rest as the most important. The keyword 'immunogenicity' and its derivatives have been more researched for the new mRNA vaccines, while thrombosis has been more studied for conventional vaccines. The massive scientific production generated on COVID-19 vaccines in only two years has shown the enormous gravity of the pandemic and the extreme urgency to find a solution. This high scientific production and the main keywords found for the mRNA vaccines indicate the great potential that these vaccines have against COVID-19 and future infectious diseases. Moreover, this study provides valuable information for guiding future research lines and promoting international collaboration for an effective solution.
Project description:Since the first successful application of messenger ribonucleic acid (mRNA) as a vaccine agent in a preclinical study nearly 30 years ago, numerous advances have been made in the field of mRNA therapeutic technologies. This research uncovered the unique favorable characteristics of mRNA vaccines, including their ability to give rise to non-toxic, potent immune responses and the potential to design and upscale them rapidly, making them excellent vaccine candidates during the coronavirus disease 2019 (COVID-19) pandemic. Indeed, the first two vaccines against COVID-19 to receive accelerated regulatory authorization were nucleoside-modified mRNA vaccines, which showed more than 90% protective efficacy against symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection alongside tolerable safety profiles in the pivotal phase III clinical trials. Real-world evidence following the deployment of global vaccination campaigns utilizing mRNA vaccines has bolstered clinical trial evidence and further illustrated that this technology can be used safely and effectively to combat COVID-19. This unprecedented success also emphasized the broader potential of this new drug class, not only for other infectious diseases, but also for other indications, such as cancer and inherited diseases. This review presents a brief history and the current status of development of four mRNA vaccine platforms, nucleoside-modified and unmodified mRNA, circular RNA, and self-amplifying RNA, as well as an overview of the recent progress and status of COVID-19 mRNA vaccines. We also discuss the current and anticipated challenges of these technologies, which may be important for future research endeavors and clinical applications.
Project description:Since its outbreak in late 2019, the novel coronavirus disease 2019 (COVID-19) has spread to every continent on the planet. The global pandemic has affected human health and socioeconomic status around the world. At first, the global response to the pandemic was to isolate afflicted individuals to prevent the virus from spreading, while vaccine development was ongoing. The genome sequence was first presented in early January 2020, and the phase I clinical trial of the vaccine started in March 2020 in the United States using novel lipid-based nanoparticle (LNP), encapsulated with mRNA termed as mRNA-1273. Till now, various mRNA-based vaccines are in development, while one mRNA-based vaccine got market approval from US-FDA for the prevention of COVID-19. Previously, mRNA-based vaccines were thought to be difficult to develop, but the current development is a significant accomplishment. However, widespread production and global availability of mRNA-based vaccinations to combat the COVID-19 pandemic remains a major challenge, especially when the mutations continually occur on the virus (e.g., the recent outbreaks of Omicron variant). This review elaborately discusses the COVID-19 pandemic, the biology of SARS-CoV-2 and the progress of mRNA-based vaccines. Moreover, the review also highlighted a detailed description of mRNA delivery technologies and the application potential in controlling other life-threatening diseases. Therefore, it provides a comprehensive view and multidisciplinary insights into mRNA therapy for broader audiences.