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J Leukoc Biol. 2011 Aug;90(2):389-98. doi: 10.1189/jlb.0211068. Epub 2011 May 17.

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

Author information

1
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.

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.

PMID:
21586676
PMCID:
PMC3133438
DOI:
10.1189/jlb.0211068
[Indexed for MEDLINE]
Free PMC Article

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