Phase 2 clinical trial of attenuated Salmonella enterica serovar typhi oral live vector vaccine CVD 908-htrA in U.S. volunteers.

Abstract

Salmonella enterica serovar Typhi strain CVD 908-htrA is a live attenuated strain which may be useful as an improved oral typhoid vaccine and as a vector for cloned genes of other pathogens. We conducted a phase 2 trial in which 80 healthy adults received one of two dosage levels of CVD 908-htrA in a double-blind, placebo-controlled, crossover study. There were no differences in the rates of side effects among volunteers who received high-dose vaccine (4.5 x 10(8) CFU), lower-dose vaccine (5 x 10(7) CFU), or placebo in the 21 days after vaccination, although recipients of high-dose vaccine (8%) had more frequent diarrhea than placebo recipients (0%) in the first 7 days. Seventy-seven percent and 46% of recipients of high- and lower-dose vaccines, respectively, briefly excreted vaccine organisms in their stools. All blood cultures were negative. Antibody-secreting cells producing antilipopolysaccharide (LPS) immunoglobulin A (IgA) were detected in 100 and 92% of recipients of high- and lower-dose vaccines, respectively. Almost half the volunteers developed serum anti-LPS IgG. Lymphocyte proliferation and gamma interferon production against serovar Typhi antigens occurred in a significant proportion of vaccinees. This phase 2 study supports the further development of CVD 908-htrA as a single-dose vaccine against typhoid fever and as a possible live vector for oral delivery of other vaccine antigens.

• Authors: C O Tacket, M B Sztein, S S Wasserman, G Losonsky, K L Kotloff, T L Wyant, J P Nataro, R Edelman, J Perry, P Bedford, D Brown, S Chatfield, G Dougan, M M Levine
• Journal: Infection and immunity (Infect Immun) Vol. 68 Issue 3 Pg. 1196-201 (Mar 2000) ISSN: 0019-9567 [Print] United States
• PMID: 10678926 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Bacterial
• Bacterial Vaccines
• Heat-Shock Proteins
• Periplasmic Proteins
• Vaccines, Inactivated
• Interferon-gamma
• DegP protease
• Serine Endopeptidases

Topics

• Administration, Oral
• Adolescent
• Adult
• Antibodies, Bacterial (blood)
• Bacterial Vaccines (adverse effects, immunology)
• Cross-Over Studies
• Double-Blind Method
• Female
• Genetic Vectors
• Heat-Shock Proteins
• Humans
• Interferon-gamma (biosynthesis)
• Lymphocyte Activation
• Male
• Periplasmic Proteins
• Salmonella typhi (immunology)
• Serine Endopeptidases (genetics)
• Vaccines, Inactivated (immunology)