Structural insights into the broad protection against H1 influenza viruses by a computationally optimized hemagglutinin vaccine.

Autor: Dzimianski JV; Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA, USA., Han J; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA., Sautto GA; Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL, USA., O'Rourke SM; Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA, USA., Cruz JM; Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA, USA., Pierce SR; Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA., Ecker JW; Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA., Carlock MA; Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA., Nagashima KA; Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.; Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA., Mousa JJ; Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.; Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.; Department of Biochemistry and Molecular Biology, Franklin College of Arts and Sciences, University of Georgia, Athens, GA, USA., Ross TM; Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL, USA.; Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.; Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA., Ward AB; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA., DuBois RM; Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA, USA. rmdubois@ucsc.edu.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2023 Apr 25; Vol. 6 (1), pp. 454. Date of Electronic Publication: 2023 Apr 25.
DOI: 10.1038/s42003-023-04793-3
Abstrakt: Influenza virus poses an ongoing human health threat with pandemic potential. Due to mutations in circulating strains, formulating effective vaccines remains a challenge. The use of computationally optimized broadly reactive antigen (COBRA) hemagglutinin (HA) proteins is a promising vaccine strategy to protect against a wide range of current and future influenza viruses. Though effective in preclinical studies, the mechanistic basis driving the broad reactivity of COBRA proteins remains to be elucidated. Here, we report the crystal structure of the COBRA HA termed P1 and identify antigenic and glycosylation properties that contribute to its immunogenicity. We further report the cryo-EM structure of the P1-elicited broadly neutralizing antibody 1F8 bound to COBRA P1, revealing 1F8 to recognize an atypical receptor binding site epitope via an unexpected mode of binding.
(© 2023. The Author(s).)
Databáze: MEDLINE
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