Skip to main content
  • Poster presentation
  • Open access
  • Published:

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

Background

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.

Results

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].

Conclusions

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.

References

  1. Gravel C, Li C, Wang J, Hashem AM, Jaentschke B, Xu KW, Lorbetskie B, Gingras G, Aubin Y, Van Domselaar G, Girard M, He R, Li X: Qualitative and quantitative analyses of virtually all subtypes of influenza A and B viral mneuraminidases using antibodies targeting the universally conserved sequences. Vaccine. 2010, 28 (36): 5774-5784.

    Article  CAS  PubMed  Google Scholar 

  2. Doyle TM, Jaentschke B, Van Domselaar G, Hashem AM, Farnsworth A, Forbes NE, Li C, Wang J, He R, Brown EG, Li X: The universal epitope of influenza A viral neuraminidase fundamentally contributes to enzyme activity and viral replication. J Biol Chem. 2013, 288 (25): 18283-18289.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Doyle TM, Hashem AM, Li C, Van Domselaar G, Larocque L, Wang J, Smith D, Cyr T, Farnsworth A, He R, Hurt AC, Brown EG, Li X: Universal anti-neuraminidase antibody inhibiting all influenza A subtypes. Antiviral Res. 2013, 100 (2): 567-574.

    Article  CAS  PubMed  Google Scholar 

  4. Doyle TM, Li C, Bucher DJ, Hashem AM, Van Domselaar G, Wang J, Farnsworth A, She Y-M, Cyr T, He R, Brown EG, Hurt AC, Li X: A monoclonal antibody targeting a highly conserved epitope in influenza B neuraminidase provides protection against drug resistant strains. Biochem Biophys Res Commun. 2013, 441 (1): 226-229.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xuguang Li.

Rights and permissions

Open Access  This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.

The Creative Commons Public Domain Dedication waiver (https://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article

Doyle, T.M., Hashem, A.M., Li, C. et al. A universal monoclonal antibody protects against all influenza A and B viruses by targeting a highly conserved epitope in the viral neuraminidase. BMC Genomics 15 (Suppl 2), P8 (2014). https://0-doi-org.brum.beds.ac.uk/10.1186/1471-2164-15-S2-P8

Download citation

  • Published:

  • DOI: https://0-doi-org.brum.beds.ac.uk/10.1186/1471-2164-15-S2-P8

Keywords