Enhancement by ampicillin of antibody responses induced by a protein antigen and a DNA vaccine carried by live-attenuated Salmonella enterica serovarTyphi

Live-attenuated Salmonella species are effective carriers of microbial anti gens and DNA vaccines. In a mouse model, the immunoglobulin M (IgM) and tot al antibody levels directed toward the lipopolysaccharide of Salmonella ent erica serovar Typhi were significantly enhanced at day 21 after oral immuni zation with live-attenuated serovar Typhi (strain Ty21a) when ampicillin wa s concomitantly administered (P < 0.05 and P < 0.005, respectively). The he at-killed Ty21a-stimulated lymphocyte proliferation indices for the ampicil lin group at day 21 were significantly higher than those for the normal sal ine (NS) group (P < 0.005, P < 0.001, and P < 0.01) for all three doses of antigen (10(4), 10(5), and 10(6) heat-killed Ty21a per well, respectively). The 50% lethal doses for mice from the ampicillin and NS groups immunized with Ty21a with pBR322 after wild-type serovar Typhi challenge on day 24 we re 3.4 x 10(7) and 5.0 x 10(6) CFU, respectively. The fecal bacterial count s for the ampicillin group at days 1, 3, and 5 were significantly lower tha n those for the NS group (P < 0.01, P < 0.01, and P < 0.05, respectively), and there was a trend toward recovery of Ty21a in a larger number of mice f rom the ampicillin group than from the NS group. Furthermore, the IgG2a lev els directed toward tetanus toroid were significantly enhanced at days 7 an d 21 after oral immunization with Ty21a that carried the fragment c of teta nus toroid when ampicillin was concomitantly administered (P < 0.05 and P < 0.005, respectively), and the IgM and total hepatitis B surface antibody l evels were significantly enhanced at days 7 (P < 0.005 and P < 0.05, respec tively) and 21 (P < 0.01 and P < 0.05, respectively) after oral immunizatio n with Ty21a that carried the DNA vaccine that encodes hepatitis B surface antigen when ampicillin was concomitantly administered, The present observa tion may improve the efficacy of the protein antigens and DNA vaccines carr ied in live-attenuated bacteria, and further experiments should be carried out to determine the best antibiotics and dosage regimen to be used, as wel l as the best carrier system for individual protein antigens and DNA vaccin es.