In vivo evidence of immunological masking of the Vibrio cholerae O antigen of a hybrid Salmonella typhi Ty21a-Vibrio cholerae oral vaccine in humans

Abstract

The immunogenicity of the live oral hybrid vaccine organism Salmonella typhi Ty21a/V. cholerae Inaba (EX210) following its growth in media containing variable concentrations of supplemental galactose was examined in human volunteer subjects. The local intestinal IgA-specific antibody responses to both typhoid and cholera lipopolysaccharide (LPS) preparations were determined. It was observed that the immunogenicity of the galactose-independent Vibrio cholerae O antigen in vivo was dependent upon the variation in galactose-dependent long chain S. typhi O antigen production which was directly proportional to the media galactose concentration. It is likely that this observation was a result of steric hindrance of the presentation of the V. cholerae O antigen by S. typhi Ty21a in the presence of the longer, immunodominant S. typhi Ty21a O antigen. This observation may have relevance to the use of S. typhi vectors in vaccine development involving the presentation of LPS-associated heterologous antigens.