SplitCore Technology Allows Efficient Production of Virus-Like Particles Presenting a Receptor-Contacting Epitope of Human IgE

A. Zh Baltabekova, Zh S. Shagyrova, A. S. Kamzina, M. Voykov, Ye Zhiyenbay, E. M. Ramanculov, A. V. Shustov

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Immunoglobulin E (IgE) plays a central role in type I hypersensitivity including allergy and asthma. Novel treatment strategy envisages development of a therapeutic vaccine designed to elicit autologous blocking antibodies against the IgE. We sought to develop an IgE-epitope antigen that induces antibodies against a receptor-contacting epitope on human IgE molecule. We designed the VLP immunogens which utilize hepatitis B virus core protein (HBcAg) as a carrier, and present arrays of the receptor-contacting epitopes of the human IgE on their surfaces. FG loop from the IgE domain Cε3 was engineered into the HBcAg. Two constructs explore a well-established approach of insertion into a main immunodominant region of the HBcAg. Third construct is different in that the carrier is produced in a form of an assembly of two polypeptide chains which upon expression remain associated in a stable VLP-forming subunit (SplitCore technology). No VLPs were isolated from E.coli expressing the IgE-epitope antigens with contiguous sequences. On the contrary, the SplitCore antigen carrying the FG loop efficiently formed the VLPs. Immunization of mice with the VLPs presenting receptor-contacting epitope of the IgE elicited antibodies recognizing the human IgE in ELISA.

Original languageEnglish
Pages (from-to)746-755
Number of pages10
JournalMolecular Biotechnology
Volume57
Issue number8
DOIs
Publication statusPublished - Apr 3 2015

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Keywords

  • Allergy
  • Hepatitis B capsid protein
  • Immunoglobulin E
  • SplitCore
  • Therapeutic vaccine
  • Virus-like particles

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Molecular Biology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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