Enhancement of humoral and protective immune response induced by live-attenuated Salmonella typhi by ampicillin

Efficacy of live-attenuated Salmonella vaccines delivered by the mucosal ro ute is limited by the dose and interference from mucosal flora of the alime ntary tract. In a mouse model, the total antibody response towards lipopoly saccharide of S. typhi was significantly enhanced at day 21 post-immunizati on with live-attenuated S. typhi (Ty21a) when ampicillin was concomitantly administered (p<0.005), and the lethal dose 50 of mice in the ampicillin an d control groups immunized with Ty21a after wild-type S. typhi challenge on day 24 was 4x10(7) and 1x10(7), respectively. The faecal bacterial counts of the ampicillin group at days 1 and 3 were significantly lower than those of the control group (p<0.01 and <0.05). On day I, the number of mice with greater than or equal to 10 Ty21a colonies isolated from the spleen was si gnificantly higher in the ampicillin group than the control group (p<0.05). Furthermore, on the same day, Ty21a was isolated from the faeces of three mice from the ampicillin group, but only one from the control group. We con clude that ampicillin may have enhanced the humoral and protective immune r esponses by giving the Ty21a a selective advantage over the normal bacteria l flora. This concept of antibiotic enhancement of immunization could have important implications for other live-attenuated vaccines, as well as the d elivery of microbial antigens and DNA vaccines by live-attenuated Salmonell a carriers.