Differential recognition of influenza A virus H1N1 neuraminidase by DNA vaccine-induced antibodies in pigs and ferrets

Frontiers in Immunology

Immunology

Ola Blixt¹  Christine Stephen²  Christian Risinger³  Isik Somuncu Johansen⁴  Charlotta Polacek⁵  Ria Lassaunière⁵  Vithiagaran Gunalan⁵  Jeanette Linnea Tingstedt⁶  Anders Fomsgaard⁶ 

[1]Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark

[2]Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, United States

[3]Department of Chemistry, University of Copenhagen, Copenhagen, Denmark

[4]Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark

[5]Research Unit of Infectious Diseases, Clinical Institute, University of Southern Denmark, Odense, Denmark

[6]Virus Research & Development Laboratory, Department of Virus & Microbiological Special Diagnostics Statens Serum Institut, Copenhagen, Denmark

[7]Virus Research & Development Laboratory, Department of Virus & Microbiological Special Diagnostics Statens Serum Institut, Copenhagen, Denmark

[8]Research Unit of Infectious Diseases, Clinical Institute, University of Southern Denmark, Odense, Denmark

关键词: influenza;    neuraminidase;    vaccines;    DNA vaccine;    antibodies;    epitope mapping;    neuraminidase inhibition;    ELLA;   

DOI  :  10.3389/fimmu.2023.1200718

 received in 2023-04-05, accepted in 2023-05-12,  发布年份 2023

来源: Frontiers

【 摘 要 】

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 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.

【 授权许可】

Unknown   
Copyright © 2023 Tingstedt, Stephen, Risinger, Blixt, Gunalan, Johansen, Fomsgaard, Polacek and Lassaunière