Differences in cross-protection in rats immunized with the B subunits of cholera toxin and Escherichia coli heat-labile toxin

Abstract

Although cholera toxin (CT), Escherichia coli heat-labile toxin (LT), and their B subunits are known to be immunologically related, the ability of each to raise an antitoxin response that provides equally strong cross-protection against active challenge with pure heterologous toxin has not been examined previously. We immunized rats with pure preparations of the B subunits of human LT, porcine LT, and CT. Immunization with either of the LT B subunits raised greater than or equal to fourfold increases in specific mucosal immunoglobulin A antitoxin titers to homologous and heterologous LT and CT B subunits, thereby providing strong protection against active challenge in ligated ileal loops with all three respective holotoxins and with a viable LT-producing E. coli strain. In contrast, immunization with the CT B subunit raised a greater than or equal to fourfold increase in antitoxin titers only to itself and provided strong protection only against challenge with the CT holotoxin. Conjugation of the CT B subunit with the E. coli heat-stable toxin by the carbodiimide reaction yielded a cross-linked immunogen with equal antigenicity for both components; immunization with this conjugate raised greater than or equal to fourfold increases in antitoxin titers to both components, but it provided significant protection only against challenge with a viable heat-stable toxin-producing E. coli strain and not to an LT-producing E. coli strain. These observations indicate that immunization with the LT B subunits raises a heterologous antitoxin response that extends to the CT B subunit, thereby providing equally strong protection against LT and CT; however, immunization with the CT B subunit raises principally a homologous antitoxin response, so that this immunogen provides strong protection only against CT.