Source:http://linkedlifedata.com/resource/pubmed/id/20600501
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
34
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pubmed:dateCreated |
2010-7-26
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pubmed:abstractText |
The Ligand Epitope Antigen Presentation System (LEAPS) converts a peptide containing a T cell epitope as small as 8 amino acids into an immunogen and directs the nature of the subsequent response. Tandem synthesis of the J peptide (a peptide from the beta-2-microglobulin) with peptides of 15 or 30 amino acids from HSV-1 or HIV made them immunogenic and promoted Th1 immune responses. Immunization of A/J or C57BL/6 mice with J-LEAPS heteroconjugates containing an epitope from the HSV-1 glycoprotein D (JgD) or an epitope from the HIV gag protein (JH) emulsified with Seppic ISA51 induced increased levels of IL-12p70 by day 3 and increased levels of interferon gamma (IFN-gamma) on days 10 and 24. Interestingly, levels of IL-10, TNF-alpha, and IL-6 did not change. Neither the H nor the gD peptides alone elicited responses and only weak responses followed immunization with the J peptide. Bone marrow (BM) cells became CD86 and CD11c positive within 48 h of treatment with JgD or JH. JH or JgD treatment promoted IL-12p70 production and expression of CD8 denoting the maturation and activation of a subclass of myeloid DCs. Pure cultures of immature myeloid DCs also responded to JgD treatment, forming clusters, developing dendrites, and producing IL-12p70 within 24 h. The JH or JgD treated bone marrow cells (JgD-DC) were necessary and sufficient to activate splenic T cells to produce IFN-gamma and the JgD-DC provided an antigen specific booster response to T cells from JgD immunized mice. Adoptive transfer of JgD-DC was also sufficient to initiate protective antigen specific immunity from lethal challenge with HSV-1. The J-LEAPS vaccines appear to act as an adjuvant and immunogen on DC precursors in a unique manner to promote activation and maturation into IL-12p70 producing DCs which then can initiate sufficient Th1 immune responses to elicit protection without production of acute phase cytokines.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes, T-Lymphocyte,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-12,
http://linkedlifedata.com/resource/pubmed/chemical/Viral Envelope Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Viral Vaccines,
http://linkedlifedata.com/resource/pubmed/chemical/gag Gene Products, Human...,
http://linkedlifedata.com/resource/pubmed/chemical/glycoprotein D, Human herpesvirus 1
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1873-2518
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 2010 Elsevier Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
2
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pubmed:volume |
28
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5533-42
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pubmed:meshHeading |
pubmed-meshheading:20600501-Adoptive Transfer,
pubmed-meshheading:20600501-Animals,
pubmed-meshheading:20600501-Antigen Presentation,
pubmed-meshheading:20600501-Cells, Cultured,
pubmed-meshheading:20600501-Dendritic Cells,
pubmed-meshheading:20600501-Epitopes, T-Lymphocyte,
pubmed-meshheading:20600501-Female,
pubmed-meshheading:20600501-Herpes Simplex,
pubmed-meshheading:20600501-Herpesvirus 1, Human,
pubmed-meshheading:20600501-Interferon-gamma,
pubmed-meshheading:20600501-Interleukin-12,
pubmed-meshheading:20600501-Mice,
pubmed-meshheading:20600501-Mice, Inbred A,
pubmed-meshheading:20600501-Mice, Inbred C57BL,
pubmed-meshheading:20600501-Th1 Cells,
pubmed-meshheading:20600501-Viral Envelope Proteins,
pubmed-meshheading:20600501-Viral Vaccines,
pubmed-meshheading:20600501-gag Gene Products, Human Immunodeficiency Virus
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pubmed:year |
2010
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pubmed:articleTitle |
J-LEAPS vaccines initiate murine Th1 responses by activating dendritic cells.
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pubmed:affiliation |
Northeastern Ohio Universities Colleges of Medicine and Pharmacy, Rootstown, OH 44272, United States.
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pubmed:publicationType |
Journal Article
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