title: Latent Membrane Protein 1 as a molecular adjuvant for single-cycle lentiviral vaccines.
abstract: BACKGROUND
  Molecular adjuvants are a promising method to enhance virus-specific immune responses and protect against HIV-1 infection. Immune activation by ligands for receptors such as CD40 can induce dendritic cell activation and maturation. Here we explore the incorporation of two CD40 mimics, Epstein Barr Virus gene LMP1 or an LMP1-CD40 chimera, into a strain of SIV that was engineered to be limited to a single cycle of infection.
  
  
  RESULTS
  Full length LMP1 or the chimeric protein LMP1-CD40 was cloned into the nef-locus of single-cycle SIV. Human and Macaque monocyte derived macrophages and DC were infected with these viruses. Infected cells were analyzed for activation surface markers by flow cytometry. Cells were also analyzed for secretion of pro-inflammatory cytokines IL-1β, IL-6, IL-8, IL-12p70 and TNF by cytometric bead array.
  
  
  CONCLUSIONS
  Overall, single-cycle SIV expressing LMP1 and LMP1-CD40 produced a broad and potent T(H)1-biased immune response in human as well as rhesus macaque macrophages and DC when compared with control virus. Single-cycle SIV-LMP1 also enhanced antigen presentation by lentiviral vector vaccines, suggesting that LMP1-mediated immune activation may enhance lentiviral vector vaccines against HIV-1.
authors: Department of Microbiology & Immunology, University of Miami Miller School of Medicine, Miami, FL, USA.
authors: Sachin
authors: S
authors: Gupta
authors: James M
authors: JM
authors: Termini
authors: Liguo
authors: L
authors: Niu
authors: Saravana K
authors: SK
authors: Kanagavelu
authors: Andrew R
authors: AR
authors: Rahmberg
authors: Richard S
authors: RS
authors: Kornbluth
authors: David T
authors: DT
authors: Evans
authors: Geoffrey W
authors: GW
authors: Stone
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