Enhanced Control of Pathogenic Simian Immunodeficiency Virus SIVmac239 Replication in Macaques Immunized with an Interleukin-12 Plasmid and a DNA Prime-Viral Vector Boost Vaccine Regimen
Abstract
DNA priming has previously been shown to elicit augmented immune responses when administered by electroporation (EP) or codelivered with a plasmid encoding interleukin-12 (pIL-12). We hypothesized that the efficacy of a DNA prime and recombinant adenovirus 5 boost vaccination regimen (DNA/rAd5) would be improved when incorporating these vaccination strategies into the DNA priming phase, as determined by pathogenic simian immunodeficiency virus SIVmac239 challenge outcome. The whole SIVmac239 proteome was delivered in 5 separate DNA plasmids (pDNA-SIV) by EP with or without pIL-12, followed by boosting 4 months later with corresponding rAd5-SIV vaccine vectors. Remarkably, after repeated low-dose SIVmac239 mucosal challenge, we demonstrate 2.6 and 4.4 log reductions of the median SIV peak and set point viral loads in rhesus macaques (RMs) that received pDNA-SIV by EP with pIL-12 compared to the median peak and set point viral loads in mock-immunized controls (P
Citation
Winstone, N.; Wilson, A.J.; Morrow, G.; Boggiano, C.; Chiuchiolo, M.J.; Lopez, M.; Kemelman, M.; Ginsberg, A.A.; Mullen, K.; Coleman, J.W.; Wu, C.D.; Narpala, S.; Ouellette, I.; Dean, H.J.; Lin, F.; Sardesai, N.Y.; Cassamasa, H.; McBride, D.; Felber, B.K.; Pavlakis, G.N.; Schultz, A.; Hudgens, M.G.; King, C.R.; Zamb, T.J.; Parks, C.L.; McDermott, A.B. Enhanced Control of Pathogenic Simian Immunodeficiency Virus SIVmac239 Replication in Macaques Immunized with an Interleukin-12 Plasmid and a DNA Prime-Viral Vector Boost Vaccine Regimen. Journal of Virology (2011) 85 (18) 9578-9587. [DOI: 10.1128/JVI.05060-11]