We have tested the efficacy of recombinant
fowl pox (rFPV) and recombinant vaccinia virus (rVV) encoding
antigens of AE clade HIV-1 in a prime-boost strategy, using both systemic and mucosal delivery routes. Of the various
vaccine routes tested, intranasal/intramuscular (i.n./i.m.) AE FPV/AE VV prime-boosting generated the highest mucosal and systemic T cell responses. Peak mucosal T cell responses occurred as early as 3 days post-boost vaccination. In contrast only low systemic responses were observed at this time with the peak response occurring at day 7. Current data also revealed that, due to better uptake of the rFPV, intranasal viral priming was much more effective than intranasal
rDNA priming tested previously. The i.m./i.m. prime-boost delivery also generated strong systemic but poor mucosal responses to Gag
peptides. Interestingly, the
oral administration of AE FPV followed by i.m. AE VV delivery elicited strong systemic responses to sub-dominant Pol 1
peptides that were absent in mice that received
vaccine by other routes. Moreover, priming with AE FPV co-expressing
cytokine IL-12 significantly enhanced the T cell responses to target
antigens, whilst co-expression of IFNgamma decreased these responses. The results also indicated that the route of inoculation and the
vaccine vector combination could radically influence not only the magnitude but also the
antigen specificity of the immune response generated. Further, in contrast to the generally protracted HIV
rDNA/rFPV multiple delivery prime-boosting, this single rFPV prime and rVV boost approach was more flexible and generated excellent mucosal and systemic immune responses to
HIV vaccine antigens.