| EBV LMP1, a viral mimic of CD40, activates dendritic cells and functions as a molecular adjuvant when incorporated into an HIV vaccine. | |
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MedLine Citation:
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PMID: 21586676 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Sachin Gupta; James M Termini; Liguo Niu; Saravana K Kanagavelu; Helena Schmidtmayerova; Victoria Snarsky; Richard S Kornbluth; Geoffrey W Stone |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-5-17 |
Journal Detail:
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Title: Journal of leukocyte biology Volume: - ISSN: 1938-3673 ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-5-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8405628 Medline TA: J Leukoc Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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*Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, Florida, USA; and. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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