Nanoparticle display of neuraminidase elicits enhanced antibody responses and protection against influenza A virus challenge.

Autor: Pascha MN; Section of Virology, Division of Infectious Diseases & Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands., Ballegeer M; VIB Center for Medical Biotechnology, VIB, 9052, Ghent, Belgium.; Department of Biochemistry and Microbiology, Ghent University, 9052, Ghent, Belgium., Roelofs MC; Structural Biochemistry, Bijvoet Centre for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Utrecht, The Netherlands., Meuris L; VIB Center for Medical Biotechnology, VIB, 9052, Ghent, Belgium.; Department of Biochemistry and Microbiology, Ghent University, 9052, Ghent, Belgium., Albulescu IC; Section of Virology, Division of Infectious Diseases & Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands., van Kuppeveld FJM; Section of Virology, Division of Infectious Diseases & Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands., Hurdiss DL; Section of Virology, Division of Infectious Diseases & Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands., Bosch BJ; Section of Virology, Division of Infectious Diseases & Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands., Zeev-Ben-Mordehai T; Structural Biochemistry, Bijvoet Centre for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Utrecht, The Netherlands., Saelens X; VIB Center for Medical Biotechnology, VIB, 9052, Ghent, Belgium. xavier.saelens@vib-ugent.be.; Department of Biochemistry and Microbiology, Ghent University, 9052, Ghent, Belgium. xavier.saelens@vib-ugent.be., de Haan CAM; Section of Virology, Division of Infectious Diseases & Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. c.a.m.dehaan@uu.nl.
Jazyk: angličtina
Zdroj: NPJ vaccines [NPJ Vaccines] 2024 May 31; Vol. 9 (1), pp. 97. Date of Electronic Publication: 2024 May 31.
DOI: 10.1038/s41541-024-00891-3
Abstrakt: Current Influenza virus vaccines primarily induce antibody responses against variable epitopes in hemagglutinin (HA), necessitating frequent updates. However, antibodies against neuraminidase (NA) can also confer protection against influenza, making NA an attractive target for the development of novel vaccines. In this study, we aimed to enhance the immunogenicity of recombinant NA antigens by presenting them multivalently on a nanoparticle carrier. Soluble tetrameric NA antigens of the N1 and N2 subtypes, confirmed to be correctly folded by cryo-electron microscopy structural analysis, were conjugated to Mi3 self-assembling protein nanoparticles using the SpyTag-SpyCatcher system. Immunization of mice with NA-Mi3 nanoparticles induced higher titers of NA-binding and -inhibiting antibodies and improved protection against a lethal challenge compared to unconjugated NA. Additionally, we explored the co-presentation of N1 and N2 antigens on the same Mi3 particles to create a mosaic vaccine candidate. These mosaic nanoparticles elicited antibody titers that were similar or superior to the homotypic nanoparticles and effectively protected against H1N1 and H3N2 challenge viruses. The NA-Mi3 nanoparticles represent a promising vaccine candidate that could complement HA-directed approaches for enhanced potency and broadened protection against influenza A virus.
(© 2024. The Author(s).)
Databáze: MEDLINE
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