title: Candida skin test reagent as a novel adjuvant for a human papillomavirus peptide-based therapeutic vaccine.
abstract: A vaccine adjuvant that can effectively promote cell-mediated immunity is currently not available. Because of the ability of a Candida skin 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 how Candida enhances 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 with Candida, demonstrated partial maturation effects on Langerhans cells indicated by significantly up-regulated CD40 (p=0.00007) and CD80 (p<0.00001) levels, and showed T-cell proliferative capacity (p<0.00001) when presented by Langerhans cells in vitro. Interestingly, the maturation effects were due to the peptides while Candida was 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-α) of Langerhans cells treated with the vaccine or Candida alone 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 with Candida 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 or Candida pulsed 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 from Candida, and the most frequently induced cytokine was IL-12.
authors.affiliation: Department of Microbiology and Parasitology, College of Basic Medical Sciences, China Medical University, Shenyang, China. Electronic address: xlwang@mail.cmu.edu.cn.
authors.forename: Xuelian
authors.initials: X
authors.lastname: Wang
authors.forename: Hannah N
authors.initials: HN
authors.lastname: Coleman
authors.forename: Uma
authors.initials: U
authors.lastname: Nagarajan
authors.forename: Horace J
authors.initials: HJ
authors.lastname: Spencer
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nakagawa
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002175:Candida / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007801:Langerhans Cells / Q000276:immunology; D053918:Papillomavirus Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D053918:Papillomavirus Vaccines
keywords: APCs; Adjuvant; Candida; HPV; Human papillomavirus; LCs; Langerhans cells; MFI; PAMPs; PBMC; PE; PRRs; antigen presenting cells; human papillomavirus; mean fluorescence intensity; pathogen-associated molecular patterns; pattern recognition receptors.; peripheral blood mononuclear cells; phycoerythrin; qRT-PCR; quantitative real-time PCR