https://eutils.ncbi.nlm.nih.gov/entrez/eutils/efetch.fcgi?db=pubmed&id=37313410&retmode=xml&tool=Litmetric&email=readroberts32@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09 373134102023061520230615
1664-3224142023Frontiers in immunologyFront ImmunolDifferential recognition of influenza A virus H1N1 neuraminidase by DNA vaccine-induced antibodies in pigs and ferrets.12007181200718120071810.3389/fimmu.2023.1200718Neuraminidase (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 H7N1CA09 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.Copyright © 2023 Tingstedt, Stephen, Risinger, Blixt, Gunalan, Johansen, Fomsgaard, Polacek and Lassaunière.TingstedtJeanette LinneaJLVirus Research & Development Laboratory, Department of Virus & Microbiological Special Diagnostics Statens Serum Institut, Copenhagen, Denmark.Research Unit of Infectious Diseases, Clinical Institute, University of Southern Denmark, Odense, Denmark.StephenChristineCDepartment of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, United States.RisingerChristianCDepartment of Chemistry, University of Copenhagen, Copenhagen, Denmark.Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark.BlixtOlaODepartment of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark.GunalanVithiagaranVVirus Research & Development Laboratory, Department of Virus & Microbiological Special Diagnostics Statens Serum Institut, Copenhagen, Denmark.JohansenIsik SomuncuISResearch Unit of Infectious Diseases, Clinical Institute, University of Southern Denmark, Odense, Denmark.FomsgaardAndersAVirus Research & Development Laboratory, Department of Virus & Microbiological Special Diagnostics Statens Serum Institut, Copenhagen, Denmark.Research Unit of Infectious Diseases, Clinical Institute, University of Southern Denmark, Odense, Denmark.PolacekCharlottaCVirus Research & Development Laboratory, Department of Virus & Microbiological Special Diagnostics Statens Serum Institut, Copenhagen, Denmark.LassaunièreRiaRVirus Research & Development Laboratory, Department of Virus & Microbiological Special Diagnostics Statens Serum Institut, Copenhagen, Denmark.engJournal ArticleResearch Support, Non-U.S. Gov't20230529
SwitzerlandFront Immunol1015609601664-32240Vaccines, DNAEC 3.2.1.18Neuraminidase0Antibodies, Viral0Influenza VaccinesIMAnimalsSwineHumansVaccines, DNAFerretsInfluenza A Virus, H1N1 SubtypeNeuraminidasegeneticsInfluenza A Virus, H7N1 SubtypeInfluenza, HumanAntibodies, ViralInfluenza VaccinesDNA vaccineELLAantibodiesepitope mappinginfluenzaneuraminidaseneuraminidase inhibitionvaccinesAF is co-inventor on a patent application covering an influenza DNA vaccine; all rights to the vaccine have been assigned to Statens Serum Institut SSI, a Danish national not-for-profit governmental public health institute. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.2023452023512202361564220236146422023614357202311epublish37313410PMC1025832010.3389/fimmu.2023.1200718 WHO . 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