Avian influenza is one of the largest known threats to domestic poultry. Influenza outbreaks on poultry farms typically lead to the complete slaughter of the entire domestic bird population, causing severe economic losses worldwide. Moreover, there are highly pathogenic avian influenza (HPAI) strains that are able to infect the swine or human population in addition to their primary avian host and, as such, have the potential of being a global zoonotic and pandemic threat. Migratory birds, especially waterfowl, are a natural reservoir of the avian influenza virus; they carry and exchange different virus strains along their migration routes, leading to antigenic drift and antigenic shift, which results in the emergence of novel HPAI viruses. This requires monitoring over time and in different locations to allow for the upkeep of relevant knowledge on avian influenza virus evolution and the prevention of novel epizootic and epidemic outbreaks. In this review, we assess the role of migratory birds in the spread and introduction of influenza strains on a global level, based on recent data. Our analysis sheds light on the details of viral dissemination linked to avian migration, the viral exchange between migratory waterfowl and domestic poultry, virus ecology in general, and viral evolution as a process tightly linked to bird migration. We also provide insight into methods used to detect and quantify avian influenza in the wild. This review may be beneficial for the influenza research community and may pave the way to novel strategies of avian influenza and HPAI zoonosis outbreak monitoring and prevention.
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 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.
Flow cytometry is a powerful and widely used tool for the analysis of various cell populations, but its capabilities are severely limited by the need to apply correction of fluorescent signals from near or similar fluorochromes when analyzing multicolor panels. Spectral flow cytometry extends the capabilities of classical cytometry by reading the full fluorescence spectrum of fluorophores and their subsequent spectral separation. This significantly increases the number of markers analyzed in a single panel and thus allows for more in-depth studies of cell populations. In the age of big data analysis, this represents a serious advantage of spectral cytometry and can significantly increase its use in scientific and clinical practice. This review describes the principle of spectral cytometry, advantages and limitations of the method, and summarizes the newest deep immunophenotyping panels developed and validated for spectral cytometry.
Coagulation factor VIII (FVIII) is a key therapeutic protein for hemophilia A, an inherited bleeding disorder caused by FVIII deficiency or dysfunction. The development and production of FVIII-based therapeutics remains challenging due to the intrinsic complexity of FVIII biosynthesis, folding, secretion, and functional stability. Advances in the understanding of the FVIII life cycle, as well as studies of its natural homologs, have created opportunities to develop improved FVIII variants. In parallel, therapeutic strategies to restore FVIII activity have evolved from replacement therapy with exogenous FVIII to gene-based delivery of a functional F8 copy. Among these approaches, AAV-mediated gene therapy has emerged as a clinically viable platform with a generally favorable safety profile, prompting the development of multiple therapeutic candidates for hemophilia A. This review summarizes established and current knowledge of FVIII structure, biosynthesis, and immunology in the context of developing effective and clinically applicable AAV-mediated therapies for hemophilia A. Particular attention is given to engineered FVIII variants and the latest clinical findings in AAV gene therapy, as well as to long-term efficacy and safety.
Polygenic autoimmune diseases (ADs) have several common features that are caused by a complex interplay of genetic and environmental factors. Common pathophysiological mechanisms include dysregulation of the immune system, chronic inflammation, and epigenetic changes influenced by external factors. For the prediction of the genetic predisposition of AD manifestation, polygenic risk scale (PRS), or polygenic scores (PGSs), are used. Use of PRSs faces several challenges such as applicability on a specific population, performance comparison, and estimation of biological relevance based on SNP number. We compared PRS with different numbers of SNPs and tried to find the common genetic core of ADs. Our analysis revealed a list of the most common altered genes, which we annotated and interpreted. Clustering of PRS based on used genes showed that clusters of ADs remained consistent across all chosen PRS sizes. We concluded that PRS size does not have an impact on biological relevance.