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  • Open Access

A universal monoclonal antibody protects against all influenza A and B viruses by targeting a highly conserved epitope in the viral neuraminidase

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  • 1, 2, 9Email author
BMC Genomics201415 (Suppl 2) :P8

  • Published:


  • Influenza
  • MDCK Cell
  • Shannon Entropy
  • Recombinant Virus
  • H3N2 Strain


Hemagglutinin (HA) and neuraminidase (NA) are the two major surface glycoproteins of influenza viruses and the main targets of vaccine-induced antibodies (Abs). While several broadly neutralizing Abs targeting conserved epitopes in diverse HA subtypes have been isolated, NA-specific Abs could only cross-protect partially against homologous and heterologous strains from the same subtype.

Materials and methods

Comprehensive bioinformatics analyses of all publicly available full-length NA sequences using multiple alignments and Shannon entropy were conducted to identify conserved sequences in all influenza A and B viral NA [1]. Growth kinetics of wild-type or recombinant viruses with single alanine substitutions within the identified regions was then analyzed in MDCK cells. A rabbit monoclonal Ab (mAb), denoted as HCA-2, raised against one of the characterized sequences was then examined for its in vitro inhibitory effects and in vivo prophylactic efficacy against several influenza A and B strains.


Bioinformatics analyses uncovered a universally conserved 9-mer peptide amongst all influenza NA proteins (amino acids 222-230 and comprised of “ILRTQESEC”). Substitutions within this universal epitope underscored its crucial roles in viral fitness and replication [2]. Importantly, the HCA-2 mAb showed broad in vitro inhibition against multiple strains from all influenza A NA subtypes (N1-N9) and influenza B viruses from both Victoria and Yamagata genetic lineages [3, 4]. It also provided heterosubtypic protection in mice against lethal doses of H1N1 and H3N2 strains. Finally, amino acid residues I222 and E227, located in close proximity to the active site, were found to be indispensable for inhibition by this mAb [3, 4].


These findings reveal the essential role of this unique highly-conserved sequence in NA function and viral replication and indicate that it is sufficiently exposed to allow access by inhibitory antibody during the course of infection. Thus, it could represent a potential target for novel antivirals or targeted-vaccines against diverse strains of influenza A and B viruses.

Authors’ Affiliations

Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada, Ottawa, ON, Canada
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada
Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
Special Infectious Agents Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, Saudi Arabia
National Institutes for Food and Drug Control, Beijing, China
Department of Microbiology & Immunology, New York Medical College, Valhalla, NY 10595, USA
National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada
WHO Collaborating Centre for Reference and Research on Influenza, 10 Wreckyn St, North Melbourne, Victoria, 3051, Australia
Emerging Pathogens Research Centre, University of Ottawa, Ottawa, ON, Canada


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© Doyle et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.