Anti-class II monoclonal antibody-targeted Vibrio cholerae TcpA pilin: Modulation of serologic response, epitope specificity, and isotype

Toxin-coregulated pilus (TCP) is a colonization factor required for cholera infection. It is not a strong immunogen when delivered in the context of w hole 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 th e addition of cholera toxin (CT) or anti-CD40 MAb to determine if the serol ogic response to TcpA could be manipulated. Anti-class II MAb-targeted TCP Influenced the anti-TCP peptide serologic response with respect to titer an d isotype. Responses to TcpA peptide 4 were induced with class II MAb-targe ted TCP and not with nontargeted TCP. Class II MAb-targeting TcpA reduced t he response to peptide 6 compared to the nontargeted TCP response. Class II MAb-targeted TcpA, if delivered with CT, enhanced the serologic response t o TcpA peptides. The effectiveness of the combination of targeted TCP and C T was reduced if anti-CD40 MAb were included in the primary immunization. T hese 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 v accines.