Ebv LMP1, a viral mimic of CD40, activates dendritic cells and functions as a molecular adjuvant when incorporated into an HIV vaccine

Sachin Gupta, James M. Termini, Liguo Niu, Saravana K. Kanagavelu, Helena Schmidtmayerova, Victoria Snarsky, Richard S. Kornbluth, Geoffrey W. Stone

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

HIV-1 does not significantly activate cellular immunity, which has made it difficult to use attenuated forms of HIV-1 as a vaccine. In contrast, EBV induces robust T cell responses in most infected individuals, perhaps as this virus contains LMP1, a viral mimic of CD40, which is a key activating molecule for DCs and macrophages. Consequently, studies were conducted using LMP1 and LMP1-CD40, a related construct formed by replacing the intracellular signaling domain of LMP1 with that of CD40. Upon electroporation into DCs, LMP1 and LMP1- CD40 mRNAs were sufficient to up-regulate costimulatory molecules and proinflammatory cytokines, indicating that these molecules can function in isolation as adjuvant- like molecules. As a first step toward an improved HIV vaccine, LMP1 and LMP1-CD40 were introduced into a HIV-1 construct to produce virions encoding these proteins. Transduction of DCs and macrophages with these viruses induced morphological changes and up-regulated costimulatory molecules and cytokine production by these cells. HIV-LMP1 enhanced the antigen-presenting function of DCs, as measured in an in vitro immunization assay. Taken together, these data show that LMP1 and LMP1-CD40 are portable gene cassettes with strong adjuvant properties that can be introduced into viruses such as HIV, which by themselves, are insufficient to induce protective cellular immunity.

Original languageEnglish (US)
Pages (from-to)389-398
Number of pages10
JournalJournal of Leukocyte Biology
Volume90
Issue number2
DOIs
StatePublished - Aug 1 2011

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Keywords

  • Antigen-presenting cell
  • Attenuated viral vaccines
  • Macrophages

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

Gupta, S., Termini, J. M., Niu, L., Kanagavelu, S. K., Schmidtmayerova, H., Snarsky, V., Kornbluth, R. S., & Stone, G. W. (2011). Ebv LMP1, a viral mimic of CD40, activates dendritic cells and functions as a molecular adjuvant when incorporated into an HIV vaccine. Journal of Leukocyte Biology, 90(2), 389-398. https://doi.org/10.1189/jlb.0211068