Safety and immunogenicity of attenuated Salmonella enterica serovar Typhimurium delivering an HIV-1 Gag antigen via the Salmonella Type III secretion system

Vaccine. 2006 Sep 11;24(37-39):6216-24. doi: 10.1016/j.vaccine.2006.05.094. Epub 2006 Jun 13.


Background: CKS257 (Salmonella typhimurium SL1344 DeltaphoP/phoQDelta aroA Deltaasd DeltastrA/strB pSB2131) is a live oral vaccine vector expressing HIV Gag.

Methods: HIV Gag was expressed as a fusion protein of a Salmonella Type III secretion system protein SopE, from a balanced lethal asd-based plasmid. Eighteen healthy adults were given single escalating oral doses of 5 x 10(6) to 1 x 10(10)CFU of CKS257 and were monitored for clinical events, shedding and immune responses.

Results: Adverse events were mild except at the highest dose. Volunteers shed the organism an average of 5.1 days (range 0-13 days). Eighty-three percent (15/18) of subjects had a mucosal immune response to Salmonella LPS and flagella by IgA ELISPOT assay. Seventy-two percent (13/18) of subjects seroconverted to Salmonella antigens. No volunteer had a response to recombinant Gag as measured by serology, IgA ELISPOT, or immediate ex vivo gamma-interferon ELISPOT response to Gag peptide pools. Two volunteers responded to Gag peptides by IL-2 ELISPOT, and 4 of 10 volunteers receiving >or=5 x 10(8)CFU had a response to HIV peptides in a cultured gamma-interferon ELISPOT assay.

Conclusions: Although immunogenicity of the HIV antigen needs augmentation, the attenuated Salmonella strain proved to be an excellent platform for vaccine development.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / adverse effects
  • AIDS Vaccines / genetics
  • AIDS Vaccines / immunology*
  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins / adverse effects
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology*
  • Dose-Response Relationship, Immunologic
  • Gene Products, gag / genetics
  • Gene Products, gag / immunology*
  • HIV Core Protein p24 / immunology
  • HIV Infections / immunology
  • HIV Infections / prevention & control
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Molecular Sequence Data
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Salmonella Vaccines / adverse effects
  • Salmonella Vaccines / genetics
  • Salmonella Vaccines / immunology*
  • Salmonella typhi / genetics
  • Salmonella typhi / immunology*
  • Salmonella typhi / physiology
  • U937 Cells
  • Vaccines, Attenuated / adverse effects
  • Vaccines, Attenuated / genetics
  • Vaccines, Attenuated / immunology


  • AIDS Vaccines
  • Bacterial Proteins
  • Gene Products, gag
  • HIV Core Protein p24
  • Recombinant Fusion Proteins
  • Salmonella Vaccines
  • SopE protein, Salmonella
  • Vaccines, Attenuated