title: Safety and immunogenicity of attenuated Salmonella enterica serovar Typhimurium delivering an HIV-1 Gag antigen via the Salmonella Type III secretion system.
abstract: 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.
authors.affiliation: Infectious Disease Division, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, GRJ 504, Boston, MA 02114, USA.
authors.forename: Camille N
authors.initials: CN
authors.lastname: Kotton
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Lankowski
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Scott
authors.forename: David
authors.initials: D
authors.lastname: Sisul
authors.forename: Li Mei
authors.initials: LM
authors.lastname: Chen
authors.forename: Katherine
authors.initials: K
authors.lastname: Raschke
authors.forename: Genevieve
authors.initials: G
authors.lastname: Borders
authors.forename: Mark
authors.initials: M
authors.lastname: Boaz
authors.forename: Aggeliki
authors.initials: A
authors.lastname: Spentzou
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Galán
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Hohmann
mesh_terms: D016915:AIDS Vaccines / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D016655:HIV Core Protein p24 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D022562:Salmonella Vaccines / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D012485:Salmonella typhi / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D020298:U937 Cells; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D001426:Bacterial Proteins; D015683:Gene Products, gag; D016655:HIV Core Protein p24; D011993:Recombinant Fusion Proteins; D022562:Salmonella Vaccines; C103987:SopE protein, Salmonella; D014613:Vaccines, Attenuated