Inactivated Vibrio cholerae strains that express TcpA via the toxT-139F allele induce antibody responses against TcpA

Abstract

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 Vibrio cholerae 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, V. cholerae strains that contain toxT-139F allele have been reported to produce CT and TCP under simple laboratory culture conditions. Thus, V. cholerae strains that express TCP via the toxT-139F allele have been expected to induce TCP-specific antibody responses. As anticipated, V. cholerae strains that expressed TCP through the toxT-139F allele elicited antibody responses against TCP when the inactivated bacteria were delivered to a mouse model. TCP-expressing V. cholerae strains that have been used in inactivated OCVs were further developed and shown that they effect an antibody response against TcpA in vivo, suggesting that V. cholerae strains with the toxT-139F allele are excellent candidates for cholera vaccines.