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

Background: CKS257 (Sabnonella typhimurium SL1344 Delta phoP/phoQ Delta aroA Delta asd Delta strA/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 >= 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. (c) 2006 Elsevier Ltd. All rights reserved.