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Open Access Research

Latent Membrane Protein 1 as a molecular adjuvant for single-cycle lentiviral vaccines

Sachin Gupta1, James M Termini1, Liguo Niu14, Saravana K Kanagavelu1, Andrew R Rahmberg2, Richard S Kornbluth3, David T Evans2 and Geoffrey W Stone1*

Author Affiliations

1 Department of Microbiology & Immunology, University of Miami Miller School of Medicine, Miami, FL, USA

2 Department of Microbiology and Molecular Genetics, Harvard Medical School, New England Primate Research Center, Southborough, MA, USA

3 Multimeric Biotherapeutics, Inc., La Jolla, CA, USA

4 University of North Carolina School of Medicine, 3302 Michael Hooker Research Building, Chapel Hill, NC, 27599, USA

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Retrovirology 2011, 8:39  doi:10.1186/1742-4690-8-39

Published: 18 May 2011

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 TH1-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.