Universal anti-neuraminidase antibody inhibiting all influenza A subtypes

• Published in: Antiviral research 2013-11, Vol.100 (2), p.567-574
• Main Authors: Doyle, Tracey M., Hashem, Anwar M., Li, Changgui, Van Domselaar, Gary, Larocque, Louise, Wang, Junzhi, Smith, Daryl, Cyr, Terry, Farnsworth, Aaron, He, Runtao, Hurt, Aeron C., Brown, Earl G., Li, Xuguang
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - isolation & purification; Antibodies, Viral - immunology; Antibodies, Viral - isolation & purification; Antiviral agents; Biological and medical sciences; Cross Protection; Disease Models, Animal; Epitopes, B-Lymphocyte - immunology; Female; Human viral diseases; Infectious diseases; Influenza A Virus, H1N1 Subtype - immunology; Influenza A Virus, H3N2 Subtype - immunology; Medical sciences; Mice; Neuraminidase; Neuraminidase - immunology; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - prevention & control; Orthomyxoviridae Infections - virology; Pharmacology. Drug treatments; Universal antibody; Viral diseases; Viral diseases of the respiratory system and ent viral diseases; Viral Proteins - immunology
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2013.09.018

•The influenza virus neuraminidase evolves in an unpredictable fashion.•The influenza viral neuraminidases have only one universally conserved epitope which plays crucial roles in virus replication.•Monoclonal antibody targeting this epitope inhibits all 9 NA subtypes of virus. The only universally conserved sequence amongst all influenza A viral neuraminidase (NA) is located between amino acids 222–230 and plays crucial roles in viral replication. However, it remained unclear as to whether this universal epitope is exposed during the course of infection to allow binding and inhibition by antibodies. Using a monoclonal antibody (MAb) targeting this specific epitope, we demonstrated that all nine subtypes of NA were inhibited in vitro by the MAb. Moreover, the antibody also provided heterosubtypic protection in mice challenged with lethal doses of mouse-adapted H1N1 and H3N2, which represent group I and II viruses, respectively. Furthermore, we report amino acid residues I222 and E227, located in close proximity to the active site, are indispensable for inhibition by this antibody. This unique, highly-conserved linear sequence in viral NA could be an attractive immunological target for protection against diverse strains of influenza viruses.