Targeting of Influenza Viral Epitopes to Antigen-Presenting Cells by Genetically Engineered Chimeric Molecules in a Humanized NOD SCID Gamma Transfer Model

Iva I. Ivanova, Nikolina M. Mihaylova, Iliyan K. Manoylov, Dimitra Makatsori, Stefan Lolov, Maria H. Nikolova, Avgi Mamalaki, J. Prechl, Andrey I. Tchorbanov

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Antiviral DNA vaccines are a novel strategy in the vaccine development field, which basically consists of the administration of expression vectors coding viral antigen sequences into the host's cells. Targeting of conserved viral epitopes by antibody fragments specific to activating cell surface co-receptor molecules on antigen-presenting cells could be an alternative approach for inducing protective immunity. It has been shown that FcγRI on human monocytes enhances antigen presentation in vivo. Various DNA constructs, encoding a Single-chain variable antibodies (scFv) from mouse anti-human FcγRI monoclonal antibody, coupled to a sequence encoding a T- and B-cell epitope-containing influenza A virus hemagglutinin inter-subunit peptide were inserted into the eukaryotic expression vector system pTriEx-3 Neo. The constructed chimeric DNA molecules were expressed by transfected Chinese hamster ovary cells and the ability of the engineered proteins to interact with FcγRI-expressing cells was confirmed by flow cytometry. The fusion protein induced a strong signal transduction on human monocytes via FcγRI. The expression vector pTriEx-3 Neo containing the described construct was used as a naked DNA vaccine and introduced directly to experimental humanized NOD SCID gamma mice with or without boosting with the expressed fusion protein. Immunization with the generated DNA chimeric molecules and prime-boost with the expressed recombinant proteins induced significant serum levels of anti-influenza immunoglobulin G antibodies and strong cytotoxic T lymphocyte activity against influenza virus-infected cells in humanized animals.

Original languageEnglish
Pages (from-to)1056-1070
Number of pages15
JournalHuman Gene Therapy
Volume29
Issue number9
DOIs
Publication statusPublished - Sep 1 2018

Fingerprint

Antigen-Presenting Cells
Human Influenza
Epitopes
DNA Vaccines
Monocytes
DNA
Viral Antibodies
B-Lymphocyte Epitopes
Single-Chain Antibodies
Immunoglobulin Fragments
Inbred NOD Mouse
Proteins
T-Lymphocyte Epitopes
SCID Mice
Viral Antigens
Influenza A virus
Antigen Presentation
Hemagglutinins
Cell Surface Receptors
Cytotoxic T-Lymphocytes

Keywords

  • chimeric molecules
  • DNA vaccines
  • humanized NSG models
  • influenza virus

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Ivanova, I. I., Mihaylova, N. M., Manoylov, I. K., Makatsori, D., Lolov, S., Nikolova, M. H., ... Tchorbanov, A. I. (2018). Targeting of Influenza Viral Epitopes to Antigen-Presenting Cells by Genetically Engineered Chimeric Molecules in a Humanized NOD SCID Gamma Transfer Model. Human Gene Therapy, 29(9), 1056-1070. https://doi.org/10.1089/hum.abc2018.100

Targeting of Influenza Viral Epitopes to Antigen-Presenting Cells by Genetically Engineered Chimeric Molecules in a Humanized NOD SCID Gamma Transfer Model. / Ivanova, Iva I.; Mihaylova, Nikolina M.; Manoylov, Iliyan K.; Makatsori, Dimitra; Lolov, Stefan; Nikolova, Maria H.; Mamalaki, Avgi; Prechl, J.; Tchorbanov, Andrey I.

In: Human Gene Therapy, Vol. 29, No. 9, 01.09.2018, p. 1056-1070.

Research output: Contribution to journalArticle

Ivanova, II, Mihaylova, NM, Manoylov, IK, Makatsori, D, Lolov, S, Nikolova, MH, Mamalaki, A, Prechl, J & Tchorbanov, AI 2018, 'Targeting of Influenza Viral Epitopes to Antigen-Presenting Cells by Genetically Engineered Chimeric Molecules in a Humanized NOD SCID Gamma Transfer Model', Human Gene Therapy, vol. 29, no. 9, pp. 1056-1070. https://doi.org/10.1089/hum.abc2018.100
Ivanova, Iva I. ; Mihaylova, Nikolina M. ; Manoylov, Iliyan K. ; Makatsori, Dimitra ; Lolov, Stefan ; Nikolova, Maria H. ; Mamalaki, Avgi ; Prechl, J. ; Tchorbanov, Andrey I. / Targeting of Influenza Viral Epitopes to Antigen-Presenting Cells by Genetically Engineered Chimeric Molecules in a Humanized NOD SCID Gamma Transfer Model. In: Human Gene Therapy. 2018 ; Vol. 29, No. 9. pp. 1056-1070.
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