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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
34
pubmed:dateCreated
2010-7-26
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1873-2518
pubmed:author
pubmed:copyrightInfo
Copyright 2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
2
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5533-42
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
pubmed:year
2010
pubmed:articleTitle
J-LEAPS vaccines initiate murine Th1 responses by activating dendritic cells.
pubmed:affiliation
Northeastern Ohio Universities Colleges of Medicine and Pharmacy, Rootstown, OH 44272, United States.
pubmed:publicationType
Journal Article