Event Abstract

Back to Event

Human monoclonal ScFv specific to NS1 protein inhibits replication of influenza viruses across types and subtypes

Rungrueang Yodsheewan1, Santi Maneewatch2, Potjanee Srimanote3, Kanyarat Thueng-in4, Taweesak Songserm5, Fonthip Dong-din-on6, Kunan Bangphoomi7, Nitat Sookrung8, Kiattawee Choowongkomon7 and Wanpen Chaicumpa4*
  • 1 Mahidol University, Deparment of Immunology, Faculty of Medicine Siriraj Hospital, Thailand
  • 2 Mahidol University, Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Akrotiri
  • 3 Thammasat University, Graduate Program in Biomedical Science, Faculty of Allied Health Sciences, Thailand
  • 4 Mahidol University, Department of Parasitology, Faculty of Medicine Siriraj Hospital, Thailand
  • 5 Kasetsart University, Department of Veterinary Pathology, Faculty of Veterinary Medicine, Thailand
  • 6 Kasetsart University, Center for Agriculture Biotechnology, Thailand
  • 7 Kasetsart University, Department of Biochemistry, Faculty of Sciences, Thailand
  • 8 Mahidol University, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Thailand

Currently, there is a need of new anti-influenza agents that target influenza virus proteins other than ion channel M2 and neuraminidase. Non-structural protein-1 (NS1) is a highly conserved multifunctional protein which is indispensable for the virus replication cycle. In this study, fully human single chain antibody fragments (HuScFv) that bound specifically to recombinant as well as native NS1 proteins were produced from three different huscfv-phagemid transformed E. coli clones selected from a human ScFv phage display library. Results of Western blot analysis, mimotope searching/epitope identification, homology modeling and molecular docking and phage mimotope ELISA inhibition indicated that HuScFv of one E. coli clone reacted with NS1 R domain important for host innate immunity suppression while HuScFv of the other two clones bound to E domain at the sites necessary for NS1 binding to the host eIF4GI and CPSF30, respectively. The HuScFv could enter the influenza virus infected cells and interfered with the NS1 activities leading to replication inhibition of viruses belonging to various heterologous A subtypes and type B. HuScFv treated influenza virus infected cells had up-expression of IRF3 and IFN-beta genes in comparison with the controls, indicating that the antibodies could restore the host innate immune response. The fully human single chain antibodies have high potential for developing further as a safe (adjunctive) therapeutic agent for mitigating, if not abrogating, severe symptoms of influenza.

Acknowledgements

The work was supported by the Thailand Research Fund (TRF) (DPG5380001), Mahidol University and the National Research University (NRU) Project, Office of Higher Education Commission, Ministry of Education, Thailand. The human ScFv phage display library used in this study is a patented property of the National Research Council of Thailand (NRCT).

References

Hale BG, Randall RE, Ortin J, Jackson D. The multifunctional NS1 protein of influenza A viruses. J Gen Virol (2008) 89: 2359-76.
Kulkeaw K, Sakolvaree Y, Srimanote P, Tongtawe P, Maneewatch S, Sookrung N, Tungtrongchitr A, Tapchaisri P, Kurazono H, Chaicumpa W. Human monoclonal ScFv neutralize lethal Thai cobra, Naja kouathia, neurotoxin. J Proteomics (2009) 72: 270-82.
Maneewatch S, Thanongsaksrikul J, Songserm T, Thueng-in K, Kulkeaw K, Thathaisong U, Srimanote P, Tongtawe P, Tapchaisri P, Chaicumpa W. Human single chain antibodies that neutralize homologous and heterologous strains and clades of influenza A virus subtype H5N1. Antivir Ther (2009) 14: 221-30.

Keywords: NS1 protein, Epitopes, Human ScFv, influenza, Influenza Virus

Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.

Presentation Type: Abstract

Topic: Translational immunology and immune intervention

Citation: Yodsheewan R, Maneewatch S, Srimanote P, Thueng-in K, Songserm T, Dong-din-on F, Bangphoomi K, Sookrung N, Choowongkomon K and Chaicumpa W (2013). Human monoclonal ScFv specific to NS1 protein inhibits replication of influenza viruses across types and subtypes. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00520

Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.

The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.

Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.

For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.

Received: 04 Jun 2013; Published Online: 22 Aug 2013.

* Correspondence: Prof. Wanpen Chaicumpa, Mahidol University, Department of Parasitology, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand, wanpen.cha@mahidol.ac.th