title: Anti-class II monoclonal antibody-targeted Vibrio cholerae TcpA pilin: modulation of serologic response, epitope specificity, and isotype.
abstract: Toxin-coregulated pilus (TCP) is a colonization factor required for cholera infection. It is not a strong immunogen when delivered in the context of whole cells, yet pilus subunits or TcpA derivative synthetic peptides induce protective responses. We examined the efficacy of immunizing mice with TCP conjugated to anti-class II monoclonal antibodies (MAb) with or without the addition of cholera toxin (CT) or anti-CD40 MAb to determine if the serologic response to TcpA could be manipulated. Anti-class II MAb-targeted TCP influenced the anti-TCP peptide serologic response with respect to titer and isotype. Responses to TcpA peptide 4 were induced with class II MAb-targeted TCP and not with nontargeted TCP. Class II MAb-targeting TcpA reduced the response to peptide 6 compared to the nontargeted TCP response. Class II MAb-targeted TcpA, if delivered with CT, enhanced the serologic response to TcpA peptides. The effectiveness of the combination of targeted TCP and CT was reduced if anti-CD40 MAb were included in the primary immunization. These data establish the need to understand the role of TCP presentation in the generation of B-cell epitopes in order to optimize TcpA-based cholera vaccines.
authors.affiliation: Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA.
authors.forename: J Y
authors.initials: JY
authors.lastname: Wu
authors.forename: R K
authors.initials: RK
authors.lastname: Taylor
authors.forename: W F
authors.initials: WF
authors.lastname: Wade
mesh_terms: D000276:Adjuvants, Immunologic; D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000911:Antibodies, Monoclonal / Q000276:immunology; D017951:Antigen Presentation; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D019013:CD40 Antigens; D023201:CD40 Ligand; D002772:Cholera Toxin / Q000276:immunology; D022121:Cholera Vaccines / Q000276:immunology; D005260:Female; D036781:Fimbriae Proteins; D010861:Fimbriae, Bacterial / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D018796:Immunoconjugates / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D014611:Vaccination; D014734:Vibrio cholerae / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D001425:Bacterial Outer Membrane Proteins; D019013:CD40 Antigens; D022121:Cholera Vaccines; D000949:Histocompatibility Antigens Class II; D018796:Immunoconjugates; D010446:Peptide Fragments; C085807:TcpA protein, Vibrio cholerae; D023201:CD40 Ligand; D036781:Fimbriae Proteins; D002772:Cholera Toxin