The Influenza A virus is a continuous threat to public health that causes yearly epidemics with the ever-present threat of the virus becoming the next pandemic. Due to increasing levels of resistance, several of our previously used antivirals have been rendered useless. There is a strong need for new antivirals that are less likely to be susceptible to mutations. One strategy to achieve this goal is structure-based drug development. By understanding the minute details of protein structure, we can develop antivirals that target the most conserved, crucial regions to yield the highest chances of long-lasting success. One promising IAV target is the virulence protein non-structural protein 1 (NS1). NS1 contributes to pathogenicity through interactions with numerous host proteins, and many of the resulting complexes have been shown to be crucial for virulence. In this review, we cover the NS1-host protein complexes that have been structurally characterized to date. By bringing these structures together in one place, we aim to highlight the strength of this field for drug discovery along with the gaps that remain to be filled.
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http://dx.doi.org/10.3390/v15102063 | DOI Listing |
Sci Immunol
January 2025
Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA.
Understanding the naïve B cell repertoire and its specificity for potential zoonotic threats, such as the highly pathogenic avian influenza (HPAI) H5Nx viruses, may allow prediction of infection- or vaccine-specific responses. However, this naïve repertoire and the possibility to respond to emerging, prepandemic viruses are largely undetermined. Here, we profiled naïve B cell reactivity against a prototypical HPAI H5 hemagglutinin (HA), the major target of antibody responses.
View Article and Find Full Text PDFVaccines (Basel)
January 2025
Department of Comparative Pathobiology, Purdue Institute of Inflammation, Immunology and Infectious Disease, College of Veterinary Medicine, Purdue University, 625 Harrison St., West Lafayette, IN 47907, USA.
An effective universal influenza vaccine is urgently needed to overcome the limitations of current seasonal influenza vaccines, which are ineffective against mismatched strains and unable to protect against pandemic influenza. In this study, bovine and human adenoviral vector-based vaccine platforms were utilized to express various combinations of antigens. These included the H5N1 hemagglutinin (HA) stem region or HA2, the extracellular domain of matrix protein 2 of influenza A virus, HA signal peptide (SP), trimerization domain, excretory peptide, and the autophagy-inducing peptide C5 (AIP-C5).
View Article and Find Full Text PDFVaccines (Basel)
January 2025
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China.
Background: The Influenza A virus (IAV), a pathogen affecting the respiratory system, represents a major risk to public health worldwide. Immunization remains the foremost strategy to control the transmission of IAV. The virus has two primary antigens: hemagglutinin (HA) and neuraminidase (NA).
View Article and Find Full Text PDFVaccines (Basel)
January 2025
NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
Background: Polypeptide vaccines have the potential to improve immune responses by targeting conserved and weakly immunogenic regions in antigens. This study aimed to identify and evaluate the efficacy of a novel influenza universal vaccine candidate consisting of multiple polypeptides derived from highly conserved regions of influenza virus proteins hemagglutinin (HA), neuraminidase (NA), and matrix protein 2 (M2).
Methods: Immunoinformatics tools were used to screen conserved epitopes from different influenza virus subtypes (H1N1, H3N2, H5N1, H7N9, H9N2, and IBV).
Vaccines (Basel)
January 2025
Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan.
Background/objectives: In preparation for a potential pandemic caused by the H5N1 highly pathogenic avian influenza (HPAI) virus, pre-pandemic vaccines against several viral clades have been developed and stocked worldwide. Although these vaccines are well tolerated, their immunogenicity and cross-reactivity with viruses of different clades can be improved.
Methods: To address this aspect, we generated recombinant influenza vaccines against H5-subtype viruses using two different strains of highly attenuated vaccinia virus (VACV) vectors.
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