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

BackgroundCKS257 (Salmonella typhimurium SL1344 ΔphoP/phoQΔ aroA Δasd ΔstrA/strB pSB2131) is a live oral vaccine vector expressing HIV Gag.MethodsHIV 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 × 106 to 1 × 1010 CFU of CKS257 and were monitored for clinical events, shedding and immune responses.ResultsAdverse 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 γ-interferon ELISPOT response to Gag peptide pools. Two volunteers responded to Gag peptides by IL-2 ELISPOT, and 4 of 10 volunteers receiving ≥5 × 108 CFU had a response to HIV peptides in a cultured γ-interferon ELISPOT assay.ConclusionsAlthough immunogenicity of the HIV antigen needs augmentation, the attenuated Salmonella strain proved to be an excellent platform for vaccine development.