Ability of SPI2 mutant of S. typhi to effectively induce antibody responses to the mucosal antigen enterotoxigenic E. coli heat labile toxin B subunit after oral delivery to humans

AbstractWe have evaluated an oral vaccine based on an Salmonella enteric serovar typhi (S. typhi) Ty2 derivative TSB7 harboring deletion mutations in ssaV (SPI-2) and aroC together with a chromosomally integrated copy of eltB encoding the B subunit of enterotoxigenic Escherichia coli heat labile toxin (LT-B) in volunteers. Two oral doses of 108 or 109CFU were administered to two groups of volunteers and both doses were well tolerated, with no vaccinemia, and only transient stool shedding. Immune responses to LT-B and S. typhi lipopolysaccharide were demonstrated in 67 and 97% of subjects, respectively, without evidence of anti-carrier immunity preventing boosting of LT-B responses in many cases. Further development of this salmonella-based (spi-VEC) system for oral delivery of heterologous antigens appears warranted

Phase 1 clinical trial of live attenuated Shigella dysenteriae type-1 DeltaicsA Deltaent Deltafep DeltastxA:HgR oral vaccine SC599 in healthy human adult volunteers

Twenty-eight adults received between 10(2) and 10(8)colony forming units of live Shigella dysenteriae type-1 vaccine SC599, attenuated by deletion of invasion (icsA), iron chelation (ent, fep) and shiga toxin A-subunit (stxA) genes, followed by ciprofloxacin on day 4. Dose-independent diarrhea or change in bowel habit was seen in 3 subjects, without dysentery, vaccinaemia or serious adverse events. Hematology and biochemical parameters were unchanged. Doses of 10(5) or greater induced dose-independent SD1 lipopolysaccharide-specific antibody secreting cell (ASC) responses. Geometric mean number of IgA ASCs per 10(6) PBMCs for 10(5), 10(6), 10(7) and 10(8) groups were respectively 41, 8.8, 26 and 8.5. Serum antibody responses were seen in three subjects. SC599 appears immunogenic with maximum tolerated dose greater than 10(8)CFU