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Background:  Prime boost strategies combining DNA prime followed by viral vector boost generate robust T-cell responses in murine and primate models. We report the results of the first human trial to assess the safety and immunogenicity of a DNA (pHIS-HIV-B) prime, recombinant fowl pox (FPV-HIV-B) boost regimen.

Methods:  pHIS-HIV-B contains 60% of the genomic material of NL(AD8) a subtype B variant and includes mutated forms of gag, pol, env, and tat and rev under the control of the CMV I/E promoter and humanised CpG motifs. rFPV-HIV-B contains identical gag and pol inserts. The vaccine regimen was 1mg pHIS-HIV-B DNA at weeks 0 and 4 followed by 5 x 10⁷pfu rFPV-HIV-B at week 8, all administered intramuscularly in a double blind fashion. We randomized in a 3:1 ratio to receive vaccine or matched placebo, 24 healthy individuals, at low risk of HIV infection. Primary endpoints were safety and immunogenicity determined by interferon-γ (IFN- γ) ELISpot at week 9 to a pool of 15-mer B clade Gag peptides. Secondary immunogenicity endpoints included lymphoproliferative and IFN- γ and interleukin-2 (IL-2) intracellular cytokine responses to Gag and other HIV antigens. A formal analysis was conducted when the last volunteer completed week 12.

Results:  The vaccine regimen was well tolerated, and no serious adverse events occurred. Local and systemic reactions were mild to moderate. The most common adverse event was pain on boost injection, occurring in 17 of 18 vaccine and 6 of 6 placebo recipients. There was no statistically significant difference between the active and placebo groups by IFN- γ ELISpot responses to Gag (p = 0.3). Furthermore, no consistent immunogenicity could be detected by lymphoproliferative, or intracellular cytokine responses to the range of HIV-antigens presented as either overlapping peptides, recombinant proteins, or recombinant vaccinia-infected targets. Respectively, 4 of 18 and 1 of 6 in the vaccine and placebo groups, developed a response on ELISpot, intracellular cytokine, or LPA. Further investigation revealed that DNA primed a CD4⁺-mediated IL-2 response to Gag in 4/11 vaccine recipients. Boosting by rFPV was inconsistent in these individuals.

Conclusions:  The regimen was well tolerated but not significantly immunogenic. Review of preclinical primate data suggests that the dose used, when corrected for relative surface area or body weight, may be suboptimal. Considering this and the regimen’s favorable safety profile, further investigation of the optimal dosage of the constructs is warranted.

Keywords: Vaccine; HIV-1; Immunogenicity