title: Chimeric plant virus particles administered nasally or orally induce systemic and mucosal immune responses in mice.
abstract: The humoral immune responses to the D2 peptide of fibronectin-binding protein B (FnBP) of Staphylococcus aureus, expressed on the plant virus cowpea mosaic virus (CPMV), were evaluated after mucosal delivery to mice. Intranasal immunization of these chimeric virus particles (CVPs), either alone or in the presence of ISCOM matrix, primed CPMV-specific T cells and generated high titers of CPMV- and FnBP-specific immunoglobulin G (IgG) in sera. Furthermore, CPMV- and FnBP-specific IgA and IgG could also be detected in the bronchial, intestinal, and vaginal lavage fluids, highlighting the ability of CVPs to generate antibody at distant mucosal sites. IgG2a and IgG2b were the dominant IgG subclasses in sera to both CPMV and FnBP, demonstrating a bias in the response toward the T helper 1 type. The sera completely inhibited the binding of human fibronectin to the S. aureus FnBP. Oral immunization of the CVPs also generated CPMV- and FnBP-specific serum IgG; however, these titers were significantly lower and more variable than those generated by the intranasal route, and FnBP-specific intestinal IgA was undetectable. Neither the ISCOM matrix nor cholera toxin enhanced these responses. These studies demonstrate for the first time that recombinant plant viruses have potential as mucosal vaccines without the requirement for adjuvant and that the nasal route is most effective for the delivery of these nonreplicating particles.
authors.affiliation: Axis Genetics plc, Babraham, Cambridge CB2 4AZ, United Kingdom.
authors.forename: F R
authors.initials: FR
authors.lastname: Brennan
authors.forename: T
authors.initials: T
authors.lastname: Bellaby
authors.forename: S M
authors.initials: SM
authors.lastname: Helliwell
authors.forename: T D
authors.initials: TD
authors.lastname: Jones
authors.forename: S
authors.initials: S
authors.lastname: Kamstrup
authors.forename: K
authors.initials: K
authors.lastname: Dalsgaard
authors.forename: J I
authors.initials: JI
authors.lastname: Flock
authors.forename: W D
authors.initials: WD
authors.lastname: Hamilton
mesh_terms: D018829:Adhesins, Bacterial; D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology*; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D002772:Cholera Toxin / Q000276:immunology; D017798:Comovirus / Q000235:genetics / Q000276:immunology*; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D016882:ISCOMs / Q000276:immunology; D018928:Immunity, Mucosal; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification / Q000276:immunology; D007422:Intestines / Q000276:immunology; D008168:Lung / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D013211:Staphylococcus aureus / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014621:Vagina / Q000276:immunology; D014771:Virion
chemical_list: D018829:Adhesins, Bacterial; D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D002352:Carrier Proteins; D005353:Fibronectins; D016882:ISCOMs; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic; C078635:fibronectin-binding proteins, bacterial; D002772:Cholera Toxin