Engineered dityrosine-bonding of the RSV prefusion F protein imparts stability and potency advantages
Year: 2024
Type: article
Abstract: Viral fusion proteins facilitate cellular infection by fusing viral and cellular membranes, which involves dramatic transitions from their pre- to postfusion conformations. These proteins are among the most protective viral immunogens, but they are metastable which often makes them intractable as subunit vaccine targets. Adapting a natural enzymatic reaction, we harness the structural rigidity that targeted dityrosine crosslinks impart to covalently stabilize fusion proteins in their native conformations. We show that the prefusion conformation of respiratory syncytial virus fusion protein can be stabilized with two engineered dityrosine crosslinks (DT-preF), markedly improving its stability and shelf-life. Furthermore, it has 11X greater potency as compared with the DS-Cav1 stabilized prefusion F protein in immunogenicity studies and overcomes immunosenescence in mice with simply a high-dose formulation on alum.
Source: Nature Communications
Authors: Sonal V. Gidwani, Devarshi Brahmbhatt, Aaron Zomback, Mamie Bassie, Jennifer Martinez, Jian Zhuang, John Schulze, Jason S. McLellan, Roberto Mariani, Peter Alff, Daniela Frasca, Bonnie B. Blomberg, Christopher P. Marshall, Mark A. Yondola
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,790
Funders: U.S. Department of Health and Human Services, International AIDS Vaccine Initiative, New York State Economic Development Council, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, National Institute on Aging, National Institute of Allergy and Infectious Diseases
OpenAlex ID: W4392793925