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.
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Acknowledgments
This work was supported by Grant #0112RK00352 “Study of immunogenicity of virus-like particles carrying epitopes of human immunoglobulin E” from the Ministry of Education and Science (MES) of the Republic of Kazakhstan.
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The authors declare that there are no conflicts of interest.
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Baltabekova, A.Z., Shagyrova, Z.S., Kamzina, A.S. et al. SplitCore Technology Allows Efficient Production of Virus-Like Particles Presenting a Receptor-Contacting Epitope of Human IgE. Mol Biotechnol 57, 746–755 (2015). https://doi.org/10.1007/s12033-015-9867-0
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DOI: https://doi.org/10.1007/s12033-015-9867-0