title: Chimeric hepatitis E virus-like particle as a carrier for oral-delivery.
abstract: Oral delivery with virus-like particles (VLPs) is advantageous because of the inherited entry pathway from their parental viral capsids, which enables VLP to withstand the harsh and enzymatic environment associated with human digestive tract. However, the repeat use of this system is challenged by the self-immunity. In order to overcome this problem, we engineered the recombinant capsid protein of hepatitis E virus by inserting p18 peptide, derived from the V3 loop of HIV-1 gp120, into the antibody-binding site. The chimeric VLP resembled the tertiary and quaternary structures of the wild type VLP and specifically reacted with an HIV-1 antibody against V3 loop. Different from the wild type VLP, the chimeric VLP was vulnerable to trypsin cleavage although it appeared as intact particle, suggesting that the intermolecular forces of attraction between the recombinant capsid proteins are strong enough to maintain the VLP icosahedral arrangement. Importantly, this VLP containing the V3 loop did not react with anti-HEV antibodies, in correspondence to the mutation at its antibody-binding site. Therefore, the insertion of peptides at the surface antigenic site could allow VLPs to escape pre-existing anti-HEV humoral immunity.
authors.affiliation: Department of Molecular and Cellular Biology, University of California, Davis, CA 95616, United States.
authors.forename: Pitchanee
authors.initials: P
authors.lastname: Jariyapong
authors.forename: Li
authors.initials: L
authors.lastname: Xing
authors.forename: Nienke E
authors.initials: NE
authors.lastname: van Houten
authors.forename: Tian-Cheng
authors.initials: TC
authors.lastname: Li
authors.forename: Wattana
authors.initials: W
authors.lastname: Weerachatyanukul
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hsieh
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Moscoso
authors.forename: Chun-Chieh
authors.initials: CC
authors.lastname: Chen
authors.forename: Masahiro
authors.initials: M
authors.lastname: Niikura
authors.forename: R Holland
authors.initials: RH
authors.lastname: Cheng
mesh_terms: D000284:Administration, Oral; D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D001665:Binding Sites; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D006508:Hepatitis Antibodies / Q000276:immunology; D016752:Hepatitis E virus / Q000235:genetics* / Q000276:immunology*; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000235:genetics* / Q000276:immunology*; D014612:Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D036022:Capsid Proteins; D015699:HIV Envelope Protein gp120; D006508:Hepatitis Antibodies; D011993:Recombinant Fusion Proteins; D014612:Vaccines; C514793:gp120 protein, Human immunodeficiency virus 1