Safety, infectivity, immunogenicity, and in vivo stability of two attenuated auxotrophic mutant strains of Salmonella typhi, 541Ty and 543Ty, as live oral vaccines in humans

• Published in: The Journal of clinical investigation Vol. 79; no. 3; pp. 888 - 902
• Main Authors: LEVINE, M. M, HERRINGTON, D, STOCKER, B, MURPHY, J. R, MORRIS, J. G, LOSONSKY, G, TAL, B, LINDBERG, A. A, SVENSON, S, SHAHIDA BAQAR, EDWARDS, M. F
• Format: Journal Article
• Language: English
• Published: Ann Arbor, MI American Society for Clinical Investigation 01.03.1987
• Subjects: Antibodies, Bacterial - analysis; Antigens, Bacterial - immunology; Bacteriology; Biological and medical sciences; Feces - microbiology; Fundamental and applied biological sciences. Psychology; Humans; Immunity, Cellular; Lymphocyte Activation; Microbiology; Mutation; Salmonella typhi; Salmonella typhi - immunology; Salmonella typhi - isolation & purification; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, Attenuated - adverse effects; Vaccines, Attenuated - immunology; Human; Auxotrophy; Vaccine strain; Vaccination; Single dose; Oral administration; Salmonella typhi; Cellular immunity; Typhoid; Infection; Immunoprophylaxis; Immunogenicity; Bacteriosis; Bacteria; Salmonellosis; Mutation; Attenuated strain; Escherichieae; Humoral immunity; Enterobacteriaceae
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI112899

Two Salmonella typhi mutants, 541Ty (Vi+) and 543Ty (Vi-), auxotrophic for p-aminobenzoate and adenine, were evaluated as live oral vaccines. 33 volunteers ingested single doses of 10(8), 10(9), or 10(10) vaccine organisms, while four others received two 2 X 10(9) organism doses 4 d apart. No adverse reactions were observed. Vaccine was recovered from coprocultures of 29 of 37 vaccinees (78%) and from duodenal string cultures of two; repeated blood cultures were negative. The humoral antibody response to S. typhi O, H, Vi, and lysate antigens in serum and intestinal fluid was meager. In contrast, all vaccinees manifested cell-mediated immune responses. After vaccination, 69% of vaccinees overall and 89% of recipients of doses greater than or equal to 10(9) responded to S. typhi particulate or purified O polysaccharide antigens in lymphocyte replication studies but not to antigens of other Salmonella or Escherichia coli. All individuals, postvaccination, demonstrated a significant plasma-dependent mononuclear cell inhibition of wild S. typhi.