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Candidaskin test reagent as a novel adjuvant for a human papillomavirus peptide-based therapeutic vaccine

A vaccine adjuvant that can effectively promote cell-mediated immunity is currently not available. Because of the ability of aCandidaskin test reagent injection to induce common wart regression, our group is using it as a novel adjuvant in a clinical trial of a peptide-based human papillomavirus the...

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Published in:Vaccine 2013-12, Vol.31 (49), p.5806
Main Authors: Wang, Xuelian, Coleman, Hannah N, Nagarajan, Uma, Spencer, Horace J, Nakagawa, Mayumi
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container_issue 49
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container_title Vaccine
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creator Wang, Xuelian
Coleman, Hannah N
Nagarajan, Uma
Spencer, Horace J
Nakagawa, Mayumi
description A vaccine adjuvant that can effectively promote cell-mediated immunity is currently not available. Because of the ability of aCandidaskin test reagent injection to induce common wart regression, our group is using it as a novel adjuvant in a clinical trial of a peptide-based human papillomavirus therapeutic vaccine. The goal of this current study was to investigate the mechanisms of howCandidaenhances the vaccine immune responses. Maturation effects on Langerhans cells, capacity to proliferate T-cells, expression of cytokines and pattern recognition receptors by Langerhans cells, and ability to induce Th1, Th2, and Th17 responses were investigated in healthy subjects. The vaccine, human papillomavirus peptides withCandida, demonstrated partial maturation effects on Langerhans cells indicated by significantly up-regulated CD40 (p=0.00007) and CD80 (p
doi_str_mv 10.1016/j.vaccine.2013.10.014
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Because of the ability of aCandidaskin test reagent injection to induce common wart regression, our group is using it as a novel adjuvant in a clinical trial of a peptide-based human papillomavirus therapeutic vaccine. The goal of this current study was to investigate the mechanisms of howCandidaenhances the vaccine immune responses. Maturation effects on Langerhans cells, capacity to proliferate T-cells, expression of cytokines and pattern recognition receptors by Langerhans cells, and ability to induce Th1, Th2, and Th17 responses were investigated in healthy subjects. The vaccine, human papillomavirus peptides withCandida, demonstrated partial maturation effects on Langerhans cells indicated by significantly up-regulated CD40 (p=0.00007) and CD80 (p&lt;0.00001) levels, and showed T-cell proliferative capacity (p&lt;0.00001) when presented by Langerhans cells in vitro. Interestingly, the maturation effects were due to the peptides whileCandidawas responsible for the T-cell proliferation. The cytokine profile (IL-1β, IL-6, IL-8, IL-10, IL-12p40, IL-23Ap19, IFN-γ and TNF-[alpha]) of Langerhans cells treated with the vaccine orCandidaalone showed that IL-12p40 mRNA was most frequently induced, and IL-12p70 protein was detected in the supernatants. The presence of pattern recognition receptors known to associate withCandida albicans(DC-SIGN, dectin-1, dectin-2, galectin-3, mincle, mannose receptor, Toll-like receptors-1, 2, 4, 6 and 9) were demonstrated in all subjects. On the other hand, the induction of Th1 response demonstrated by IFN-γ secretion by CD4 cells stimulated with the vaccine orCandidapulsed Langerhans cells was demonstrated only in one subject. In summary, the Langerhans cell maturation effects of the vaccine were due to the peptides while the T-cell proliferative capacity was derived fromCandida, and the most frequently induced cytokine was IL-12.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2013.10.014</identifier><language>eng</language><publisher>Kidlington: Elsevier Limited</publisher><subject>Cell growth ; Cervical cancer ; Clinical trials ; Cytokines ; Human papillomavirus ; Infections ; Lymphocytes ; Pattern recognition ; Peptides ; Vaccines</subject><ispartof>Vaccine, 2013-12, Vol.31 (49), p.5806</ispartof><rights>Copyright Elsevier Limited Dec 2, 2013</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids></links><search><creatorcontrib>Wang, Xuelian</creatorcontrib><creatorcontrib>Coleman, Hannah N</creatorcontrib><creatorcontrib>Nagarajan, Uma</creatorcontrib><creatorcontrib>Spencer, Horace J</creatorcontrib><creatorcontrib>Nakagawa, Mayumi</creatorcontrib><title>Candidaskin test reagent as a novel adjuvant for a human papillomavirus peptide-based therapeutic vaccine</title><title>Vaccine</title><description>A vaccine adjuvant that can effectively promote cell-mediated immunity is currently not available. 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Because of the ability of aCandidaskin test reagent injection to induce common wart regression, our group is using it as a novel adjuvant in a clinical trial of a peptide-based human papillomavirus therapeutic vaccine. The goal of this current study was to investigate the mechanisms of howCandidaenhances the vaccine immune responses. Maturation effects on Langerhans cells, capacity to proliferate T-cells, expression of cytokines and pattern recognition receptors by Langerhans cells, and ability to induce Th1, Th2, and Th17 responses were investigated in healthy subjects. The vaccine, human papillomavirus peptides withCandida, demonstrated partial maturation effects on Langerhans cells indicated by significantly up-regulated CD40 (p=0.00007) and CD80 (p&lt;0.00001) levels, and showed T-cell proliferative capacity (p&lt;0.00001) when presented by Langerhans cells in vitro. 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subjects Cell growth
Cervical cancer
Clinical trials
Cytokines
Human papillomavirus
Infections
Lymphocytes
Pattern recognition
Peptides
Vaccines
title Candidaskin test reagent as a novel adjuvant for a human papillomavirus peptide-based therapeutic vaccine
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