title: SplitCore Technology Allows Efficient Production of Virus-Like Particles Presenting a Receptor-Contacting Epitope of Human IgE.
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.
authors.affiliation: National Center for Biotechnology, Valikhanova 13/1, 010000, Astana, Kazakhstan.
authors.forename: A Zh
authors.initials: AZh
authors.lastname: Baltabekova
authors.forename: Zh S
authors.initials: ZhS
authors.lastname: Shagyrova
authors.forename: A S
authors.initials: AS
authors.lastname: Kamzina
authors.forename: M
authors.initials: M
authors.lastname: Voykov
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhiyenbay
authors.forename: E M
authors.initials: EM
authors.lastname: Ramanculov
authors.forename: A V
authors.initials: AV
authors.lastname: Shustov
mesh_terms: D000818:Animals; D000939:Epitopes / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D006512:Hepatitis B Core Antigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics / Q000276:immunology / Q000628:therapy; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D058425:Vaccines, Virus-Like Particle / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
chemical_list: D000939:Epitopes; D006512:Hepatitis B Core Antigens; D058425:Vaccines, Virus-Like Particle; D007073:Immunoglobulin E
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