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

• Published in: Vaccine Vol. 25; no. 21; pp. 4175 - 4182
• Main Authors: Khan, S., Chatfield, S., Stratford, R., Bedwell, J., Bentley, M., Sulsh, S., Giemza, R., Smith, S., Bongard, E., Cosgrove, C.A., Johnson, J., Dougan, G., Griffin, G.E., Makin, J., Lewis, D.J.M.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 22.05.2007; Elsevier; Elsevier Science
• Subjects: Administration, Oral; Adolescent; Adult; Allergy and Immunology; Antibodies, Bacterial - blood; Antitoxins - blood; Applied microbiology; Bacterial Toxins - genetics; Bacterial Toxins - immunology; Bacterial Vaccines - genetics; Bacterial Vaccines - immunology; Bacteriology; Biological and medical sciences; Blood - microbiology; Enterotoxigenic E. coli; Enterotoxins - genetics; Enterotoxins - immunology; Enzyme-Linked Immunosorbent Assay; Escherichia coli - immunology; Escherichia coli Proteins - genetics; Escherichia coli Proteins - immunology; ETEC; Feces - microbiology; Fundamental and applied biological sciences. Psychology; Humans; Immunoglobulin G - blood; Lymphocytes - immunology; Microbiology; Middle Aged; Miscellaneous; Oral vaccine; Protein Subunits - genetics; Protein Subunits - immunology; Salmonella; Salmonella typhi - genetics; Salmonella typhi - immunology; Salmonella typhi - isolation & purification; Typhoid; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Attenuated - genetics; Vaccines, Attenuated - immunology; Salmonella; Oral vaccine; Enterotoxigenic E. coli; Typhoid; ETEC; Human; Immune response; Vaccine; Subunit; Infection; Antigen; Toxin; Local immunity; Bacteriosis; Digestive diseases; Bacteria; Salmonellosis; Mutation; Humoral immunity; Enterobacteriaceae
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2007.03.007

We 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.