title: Chimeric recombinant hepatitis E virus-like particles as an oral vaccine vehicle presenting foreign epitopes.
abstract: Many viral and bacterial pathogens establish infections through mucosal surfaces in their initial stage. However, only a few nonreplicating molecules successfully induce strong mucosal immune reaction without the addition of adjuvants by oral administration. To overcome this difficulty, we investigated whether hepatitis E virus-like particles (HEV-VLPs) could be utilized as a carrier molecule for foreign antigenic epitopes and to stimulate mucosal immunity without the need for adjuvants. To accomplish this goal, we incorporated a B cell epitope tag, consisting of 11 amino acids at the C-terminal of HEV-VLP. The chimeric VLP showed morphology similar to that of the mature HEV virion and VLP. The inserted epitope was reactive with a specific monoclonal antibody in the VLP form, suggesting that it was exposed on the surface of the VLP. After oral administration without adjuvant, this chimeric HEV induced significant levels of specific IgG and IgA to both the inserted epitope and HEV-VLP in intestinal secretions. These humoral immune responses were observed as early as 2 weeks after the first immunization. These results suggest the potential of HEV-VLP as a mucosal vaccine carrier vehicle for the presentation of antigenic epitopes through oral administration.
authors.affiliation: Department of Virology 1, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Niikura
authors.forename: Shiki
authors.initials: S
authors.lastname: Takamura
authors.forename: Gisen
authors.initials: G
authors.lastname: Kim
authors.forename: Satoru
authors.initials: S
authors.lastname: Kawai
authors.forename: Masayuki
authors.initials: M
authors.lastname: Saijo
authors.forename: Shigeru
authors.initials: S
authors.lastname: Morikawa
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kurane
authors.forename: Tian-Cheng
authors.initials: TC
authors.lastname: Li
authors.forename: Naokazu
authors.initials: N
authors.lastname: Takeda
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yasutomi
mesh_terms: D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D006508:Hepatitis Antibodies / Q000032:analysis; D016752:Hepatitis E virus / Q000235:genetics / Q000276:immunology*; D018928:Immunity, Mucosal; D007114:Immunization; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007313:Insecta; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016865:Reassortant Viruses / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D018985:Epitopes, B-Lymphocyte; D006508:Hepatitis Antibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic