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J-LEAPS vaccines initiate murine Th1 responses by activating dendritic cells

Abstract 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 1...

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Published in:Vaccine 2010-08, Vol.28 (34), p.5533-5542
Main Authors: Taylor, P.R, Koski, G.K, Paustian, C.C, Bailey, E, Cohen, P.A, Moore, F.B.-G, Zimmerman, D.H, Rosenthal, K.S
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cited_by cdi_FETCH-LOGICAL-c509t-db04fff0549d92000796986d53465a24fbef6f3ffa84e21e07c7c19e680806f43
cites cdi_FETCH-LOGICAL-c509t-db04fff0549d92000796986d53465a24fbef6f3ffa84e21e07c7c19e680806f43
container_end_page 5542
container_issue 34
container_start_page 5533
container_title Vaccine
container_volume 28
creator Taylor, P.R
Koski, G.K
Paustian, C.C
Bailey, E
Cohen, P.A
Moore, F.B.-G
Zimmerman, D.H
Rosenthal, K.S
description Abstract 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.
doi_str_mv 10.1016/j.vaccine.2010.06.043
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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. 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All rights reserved.</rights><rights>Copyright Elsevier Limited Aug 2, 2010</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c509t-db04fff0549d92000796986d53465a24fbef6f3ffa84e21e07c7c19e680806f43</citedby><cites>FETCH-LOGICAL-c509t-db04fff0549d92000796986d53465a24fbef6f3ffa84e21e07c7c19e680806f43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=23083059$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20600501$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Taylor, P.R</creatorcontrib><creatorcontrib>Koski, G.K</creatorcontrib><creatorcontrib>Paustian, C.C</creatorcontrib><creatorcontrib>Bailey, E</creatorcontrib><creatorcontrib>Cohen, P.A</creatorcontrib><creatorcontrib>Moore, F.B.-G</creatorcontrib><creatorcontrib>Zimmerman, D.H</creatorcontrib><creatorcontrib>Rosenthal, K.S</creatorcontrib><title>J-LEAPS vaccines initiate murine Th1 responses by activating dendritic cells</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>Abstract 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. 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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. 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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.</abstract><cop>Kidlington</cop><pub>Elsevier Ltd</pub><pmid>20600501</pmid><doi>10.1016/j.vaccine.2010.06.043</doi><tpages>10</tpages></addata></record>
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identifier ISSN: 0264-410X
ispartof Vaccine, 2010-08, Vol.28 (34), p.5533-5542
issn 0264-410X
1873-2518
language eng
recordid cdi_proquest_miscellaneous_864958456
source ScienceDirect Journals
subjects Adoptive Transfer
Allergy and Immunology
Amino acids
Animals
Antigen Presentation
Applied microbiology
Binding sites
Biological and medical sciences
Bone marrow
Cells, Cultured
Dendritic cells
Dendritic Cells - immunology
Epitopes, T-Lymphocyte - immunology
Female
Fundamental and applied biological sciences. Psychology
gag Gene Products, Human Immunodeficiency Virus - immunology
Herpes Simplex - immunology
Herpes Simplex - prevention & control
Herpes simplex virus 1
Herpesvirus 1, Human - immunology
HIV
HSV
Human immunodeficiency virus
IL12
Immune system
Immunization
Interferon-gamma - immunology
Interleukin-12 - immunology
LEAPS
Ligands
Lymphocytes
Mice
Mice, Inbred A
Mice, Inbred C57BL
Microbiology
Miscellaneous
Peptides
Proteins
Studies
T cell receptors
Th1
Th1 Cells - immunology
Vaccines
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
Viral Envelope Proteins - immunology
Viral Vaccines - immunology
Virology
title J-LEAPS vaccines initiate murine Th1 responses by activating dendritic cells
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