Rational design of a plasmid DNA vaccine capable of eliciting cell-mediated immune responses to multiple HIV antigens in mice

• Published in: Vaccine 2006-05, Vol.24 (21), p.4510-4523
• Main Authors: Egan, Michael A., Megati, Shakuntala, Roopchand, Vidia, Garcia-Hand, Dorys, Luckay, Amara, Chong, Siew-Yen, Rosati, Margherita, Sackitey, Solomon, Weiner, David B., Felber, Barbara K., Pavlakis, George N., Israel, Zimra R., Eldridge, John H., Sidhu, Maninder K.
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; AIDS; Animals; Antigens; Blotting, Western; Cytomegalovirus; Deoxyribonucleic acid; Developing countries; DNA; Enzyme-Linked Immunosorbent Assay; Gene Expression; Genetic engineering; Growth hormones; HIV; HIV Antigens - immunology; HIV-1; HIV-1 - genetics; HIV-1 - immunology; Human cytomegalovirus; Human immunodeficiency virus; Human immunodeficiency virus 1; Immune response; Immunity, Cellular; Immunization; Immunogenicity; Infections; LDCs; Macaca mulatta; Mice; Monkeys & apes; Mortality; Plasmid DNA vaccine; Plasmids; Promoter Regions, Genetic; Signal transduction; Triple promoter plasmid; Vaccines; Vaccines, DNA - administration & dosage; Vaccines, DNA - genetics; Vaccines, DNA - immunology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2005.08.024

Given the importance of the HIV-specific cell-mediated immune response in the early control and resolution of HIV infection and the observed correlation between pre-challenge vaccine elicited CTL responses and post challenge outcome in SHIV/rhesus macaque experiments, we sought to identify several candidate plasmid DNA (pDNA) vaccine designs capable of eliciting robust and balanced cell-mediated immune responses to multiple HIV-1 derived antigens in mice for further vaccine development. To rationally construct candidate vaccines for immunogenicity testing, we determined the relative immunogenicity of the individual HIV-derived vaccine antigens (env, gag, pol, nef, tat and vif) and the relative strength of various transcriptional control elements (HCMV, SCMV, HSV Lap1) in Balb/c mice. Next, a number of 1-, 2-, 3- and 4-vector pDNA vaccine designs were tested for their ability to elicit HIV-1 antigen-specific CMI responses. For these studies, Balb/c mice were immunized with a fixed total pDNA vaccine dose of 100 mcg in combination with 25 mcg plasmid-based murine IL-12 and tested for the induction of HIV-1 antigen-specific CMI responses by IFN-γ ELISpot analysis. The results of this study indicate that all pDNA vaccine designs were capable of eliciting CMI responses to multiple HIV-1 antigens. As a result of this iterative comparative analysis, we have identified a number of pDNA vaccine candidates capable of eliciting potent, balanced CMI responses to multiple HIV-1 derived antigens. These results have important implications for the design and development of an efficacious vaccine for the prevention of HIV-1 infection.