Inactivated Vibrio cholerae Strains That Express TcpA via the toxT -139F Allele Induce Antibody Responses against TcpA.

Cholera remains a major global public health problem, for which oral cholera vaccines (OCVs) being a valuable strategy. Patients, who have recovered from cholera, develop antibody responses against LPS, cholera toxin (CT), toxin-coregulated pilus (TCP) major subunit A (TcpA) and other antigens; thus, these responses are potentially important contributors to immunity against infection. However, assessments of the efficacy of current OCVs, especially inactivated OCVs, have focused primarily on O-antigen-specific antibody responses, suggesting that more sophisticated strategies are required for inactivated OCVs to induce immune responses against TCP, CT, and other antigens. Previously, we have shown that the -139F allele enables strains to produce CT and TCP under simple laboratory culture conditions. Thus, we hypothesized that strains that express TCP the -139F allele induce TCP-specific antibody responses. As anticipated, strains that expressed TCP through the -139F allele elicited antibody responses against TCP when the inactivated bacteria were delivered via a mouse model. We have further developed TCP-expressing strains that have been used in inactivated OCVs and shown that they effect an antibody response against TcpA in vivo, suggesting that strains with the -139F allele are excellent candidates for cholera vaccines.