Milder FJ, Jongeneelen M, Ritschel T, Bouchier P,. Universal stabilization of the influenza hemagglutinin by structure-based redesign of the pH switch regions. Proc Natl Acad Sci U S A. 2022 Feb 8;119(6):e21153
For an efficacious vaccine immunogen, influenza hemagglutinin (HA) needs to maintain a stable quaternary structure, which is contrary to the inherently dynamic and metastable nature of class I fusion proteins. In this study, we stabilized HA with three substitutions within its pH-sensitive regions where the refolding starts. An X-ray structure reveals how these substitutions stabilize the intersubunit β-sheet in the base and form an interprotomeric aliphatic layer across the stem while the native prefusion HA fold is retained. The identification of the stabilizing substitutions increases our understanding of how the pH sensitivity is structurally accomplished in HA and possibly other pH-sensitive class I fusion proteins. Our stabilization approach in combination with the occasional back mutation of rare amino acids to consensus results in well-expressing stable trimeric HAs. This repair and stabilization approach, which proves broadly applicable to all tested influenza A HAs of group 1 and 2, will improve the developability of influenza vaccines based on different types of platforms and formats and can potentially improve efficacy.
See Also:
Latest articles in those days:
- Pathogenicity of Highly Pathogenic Avian Influenza A/H5Nx Viruses in Avian and Murine Models 5 hours ago
- [preprint]No Evidence of Anti-influenza Nucleoprotein Antibodies in Retail Milk from Across Canada (April - July 2024) 17 hours ago
- Spatial risk modelling of highly pathogenic avian influenza in France: Fattening duck farm activity matters 18 hours ago
- Coordinated One Health investigation and management of outbreaks in humans and animals caused by zoonotic avian influenza viruses 2 days ago
- Assessing the Use of Different Surveillance Components to Detect Highly Pathogenic Avian Influenza Outbreaks in Poultry in the Netherlands in Low- and High-Risk Years 2 days ago
[Go Top] [Close Window]