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Differentialrecognition ofinfluenza A virusH1N1 neuraminidase byDNA vaccine-inducedantibodies in pigsand ferrets Jeanette Linnea TingstedtChristine StephenChristian Risinger2023 год

Differential recognition of influenza A virus H1N1 neuraminidase by DNA vaccine-induced antibodies in pigs and ferrets
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Аннотация: Neuraminidase (NA) accounts for approximately 10-20% of the total glycoproteins on the surface of influenza viruses. It cleaves sialic acids on glycoproteins, which facilitates virus entry into the airways by cleaving heavily glycosylated mucins in mucus and the release of progeny virus from the surface of infected cells. These functions make NA an attractive vaccine target. To inform rational vaccine design, we define the functionality of influenza DNA vaccine-induced NA-specific antibodies relative to antigenic sites in pigs and ferrets challenged with a vaccine-homologous A/California/7/2009(H1N1)pdm09 strain. Sera collected pre-vaccination, post-vaccination and post-challenge were analyzed for antibody-mediated inhibition of NA activity using a recombinant H7N1 CA09 virus. Antigenic sites were further identified with linear and conformational peptide microarrays spanning the full NA of A/California/04/2009(H1N1)pdm09. Vaccine-induced NA-specific antibodies inhibited the enzymatic function of NA in both animal models. The antibodies target critical sites of NA such as the enzymatic site, second sialic binding site and framework residues, shown here by high-resolution epitope mapping. New possible antigenic sites were identified that potentially block the catalytic activity of NA, including an epitope recognized solely in pigs and ferrets with neuraminidase inhibition, which could be a key antigenic site affecting NA function. These findings show that our influenza DNA vaccine candidate induces NA-specific antibodies that target known critical sites, and new potential antigenic sites of NA, inhibiting the catalytic activity of NA.
Год издания: 2023
Авторы: Jeanette Linnea Tingstedt, Christine Stephen, Christian Risinger, Ola Blixt, Vithiagaran Gunalan, Işık Somuncu Johansen, Anders Fomsgaard, Charlotta Polacek, Ria Lassaunière
Издательство: Frontiers Media
Источник: Frontiers in Immunology
Ключевые слова: Influenza Virus Research Studies, Respiratory viral infections research, Microbial infections and disease research
Другие ссылки: Frontiers in Immunology (PDF)
Frontiers in Immunology (HTML)
Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (HTML)
University of Southern Denmark Research Portal (University of Southern Denmark) (HTML)
Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (PDF)
Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (HTML)
University of Southern Denmark Research Portal (University of Southern Denmark) (PDF)
University of Southern Denmark Research Portal (University of Southern Denmark) (HTML)
PubMed Central (HTML)
PubMed (HTML)