Universal Flu mRNA Vaccine: Promises, Prospects, and Problems

The seasonal flu vaccine is, essentially, the only known way to prevent influenza epidemics. However, this approach has limited efficacy due to the high diversity of influenza viruses. Several techniques could potentially overcome this obstacle. A recent first-in-human study of a chimeric hemagglutinin-based universal influenza virus vaccine demonstrated promising results. The coronavirus pandemic triggered the development of fundamentally new vaccine platforms that have demonstrated their effectiveness in humans. Currently, there are around a dozen messenger RNA and self-amplifying RNA flu vaccines in clinical or preclinical trials. However, the applicability of novel approaches for a universal influenza vaccine creation remains unclear. The current review aims to cover the current state of this problem and to suggest future directions for RNA-based flu vaccine development

Cap-Independent Circular mRNA Translation Efficiency

Recently, the mRNA platform has become the method of choice in vaccine development to find new ways to fight infectious diseases. However, this approach has shortcomings, namely that mRNA vaccines require special storage conditions, which makes them less accessible. This instability is due to the fact that the five-prime and three-prime ends of the mRNA are a substrate for the ubiquitous exoribonucleases. To address the problem, circular mRNAs have been proposed for transgene delivery as they lack these ends. Notably, circular RNAs do not have a capped five-prime end, which makes it impossible to initiate translation canonically. In this review, we summarize the current knowledge on cap-independent translation initiation methods and discuss which approaches might be most effective in developing vaccines and other biotechnological products based on circular mRNAs

Cap-Independent Circular mRNA Translation Efficiency

Recently, the mRNA platform has become the method of choice in vaccine development to find new ways to fight infectious diseases. However, this approach has shortcomings, namely that mRNA vaccines require special storage conditions, which makes them less accessible. This instability is due to the fact that the five-prime and three-prime ends of the mRNA are a substrate for the ubiquitous exoribonucleases. To address the problem, circular mRNAs have been proposed for transgene delivery as they lack these ends. Notably, circular RNAs do not have a capped five-prime end, which makes it impossible to initiate translation canonically. In this review, we summarize the current knowledge on cap-independent translation initiation methods and discuss which approaches might be most effective in developing vaccines and other biotechnological products based on circular mRNAs

The Irrecoverable Loss in Sleep on Weekdays of Two Distinct Chronotypes Can Be Equalized by Permitting a >2 h Difference in Waking Time

Background: Our work/study culture is biased towards the circadian clocks of “morning types”, whereas “evening types” are forced to advance their weekday waking times relative to weekend waking times. Since the experimental research consistently reveals a >2 h difference between these two chronotypes in the positions of their endogenous circadian phases, we hypothesized the necessity to permit a >2 h difference between them in weekday waking times to equalize their irrecoverable loss in sleep on weekdays. Methods: A total of 659 and 1106 participants of online surveys identified themselves as morning and evening types, respectively. The hypothesis was tested by applying a model of sleep–wake regulation for simulating sleep times reported by 245 lecturers of these two types, and by comparison of sleep times of these types among these lecturers and 1520 students. Results: The hypothesis was supported by results showing that, if, on weekdays, an “average” morning type wakes at 6 a.m., the equalization of the weekday sleep loss of the two chronotypes would require the waking time of an “average” evening type to be no earlier than 8 a.m. Conclusions: These results may be implemented in a model-based methodology for the correction of weekday waking times to equalize weekday sleep loss