Antigenicity of purified glutaraldehyde-treated cholera toxoid administered orally

The antigenicity of orally administered glutaraldehyde-treated cholera toxoid was investigated in healthy volunteers. Fourteen volunteers ingested two or three 2-mg doses of toxoid with saline, with the doses spaced at 28-day intervals. Thirteen other volunteers received comparable toxoid doses with NaHCO3 and milk to neutralize gastric acid. Increments in circulating antitoxin levels were used to assay the antigenicity of oral toxoid. Antitoxin was measured by adrenal cell, rabbit skin permeability factor, and passive hemagglutination assays in sera collected on days 0, 28, 35, 56, 63, and 84 after primary immunization. Adrenal cell and rabbit skin assays exhibited identical sensitivity in detecting antitoxin rises in the 27 vaccinees (19/27) and were significantly more sensitive than passive hemagglutination (11/27) (P less than 0.03). Volunteers who ingested toxoid with NaHCO3 and milk had a higher rate of seroconversion (77%) than those who received toxoid with saline (64%); they also had earlier rises in antitoxin titer and consistently higher geometric mean titers on all days tested. These studies demonstrate that purified cholera toxoid is antigenic in humans after oral administration. The possible role of oral toxoid in enhancing the protective effect of killed whole-cell vaccines can now be investigated.