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

Infect Immun. 2000 Mar;68(3):1196-201. doi: 10.1128/iai.68.3.1196-1201.2000.

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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Antibodies, Bacterial / blood
  • Bacterial Vaccines / adverse effects
  • Bacterial Vaccines / 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

Substances

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