title: Prophylactic and therapeutic vaccination using dendritic cells primed with peptide 10 derived from the 43-kilodalton glycoprotein of Paracoccidioides brasiliensis.
abstract: Vaccination with peptide 10 (P10), derived from the Paracoccidioides brasiliensis glycoprotein 43 (gp43), induces a Th1 response that protects mice in an intratracheal P. brasiliensis infection model. Combining P10 with complete Freund's adjuvant (CFA) or other adjuvants further increases the peptide's antifungal effect. Since dendritic cells (DCs) are up to 1,000-fold more efficient at activating T cells than CFA, we examined the impact of P10-primed bone-marrow-derived DC vaccination in mice. Splenocytes from mice immunized with P10 were stimulated in vitro with P10 or P10-primed DCs. T cell proliferation was significantly increased in the presence of P10-primed DCs compared to the peptide. The protective efficacy of P10-primed DCs was studied in an intratracheal P. brasiliensis model in BALB/c mice. Administration of P10-primed DCs prior to (via subcutaneous vaccination) or weeks after (via either subcutaneous or intravenous injection) P. brasiliensis infection decreased pulmonary damage and significantly reduced fungal burdens. The protective response mediated by the injection of primed DCs was characterized mainly by an increased production of gamma interferon (IFN-γ) and interleukin 12 (IL-12) and a reduction in IL-10 and IL-4 compared to those of infected mice that received saline or unprimed DCs. Hence, our data demonstrate the potential of P10-primed DCs as a vaccine capable of both the rapid protection against the development of serious paracoccidioidomycosis or the treatment of established P. brasiliensis disease.
authors.affiliation: Institute of Biomedical Sciences, Department of Microbiology, University of São Paulo, São Paulo, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Magalhães
authors.forename: K S
authors.initials: KS
authors.lastname: Ferreira
authors.forename: S R
authors.initials: SR
authors.lastname: Almeida
authors.forename: J D
authors.initials: JD
authors.lastname: Nosanchuk
authors.forename: L R
authors.initials: LR
authors.lastname: Travassos
authors.forename: C P
authors.initials: CP
authors.lastname: Taborda
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005657:Fungal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology*; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010228:Paracoccidioides / Q000276:immunology*; D010229:Paracoccidioidomycosis / Q000517:prevention & control* / Q000628:therapy*; D010446:Peptide Fragments / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D016207:Cytokines; D005657:Fungal Vaccines; D006023:Glycoproteins; C550731:P10 peptide, Paracoccidioides brasiliensis; D010446:Peptide Fragments; D022223:Vaccines, Subunit
references.citation: Nature. 1998 Mar 19;392(6673):245-52
references.pmid: 9521319
references.citation: Proc Natl Acad Sci U S A. 1978 Oct;75(10):5132-6
references.pmid: 154105
references.citation: Cancer Immunol Immunother. 2008 Jan;57(1):63-71
references.pmid: 17609951
references.citation: Mycopathologia. 2008 Apr-May;165(4-5):289-302
references.pmid: 18777635
references.citation: Exp Mol Med. 2009 Feb 28;41(2):61-6
references.pmid: 19287186
references.citation: Microbes Infect. 2008 Oct;10(12-13):1251-8
references.pmid: 18694844
references.citation: Int Immunol. 2006 Dec;18(12):1637-46
references.pmid: 17035348
references.citation: J Med Microbiol. 1994 Mar;40(3):159-64
references.pmid: 8114064
references.citation: Med Mycol. 2000 Apr;38(2):177-82
references.pmid: 10817235
references.citation: Infect Immun. 2008 Jul;76(7):3321-8
references.pmid: 18458072
references.citation: J Med Vet Mycol. 1987 Apr;25(2):107-14
references.pmid: 2439674
references.citation: Mycopathologia. 2008 Apr-May;165(4-5):209-21
references.pmid: 18777630
references.citation: Am J Respir Crit Care Med. 2000 Oct;162(4 Pt 2):S146-50
references.pmid: 11029384
references.citation: Mol Med. 2003 Sep-Dec;9(9-12):209-19
references.pmid: 15208742
references.citation: Br J Cancer. 2001 Jun 1;84(11):1564-70
references.pmid: 11384109
references.citation: J Immunol. 1988 Apr 15;140(8):2786-9
references.pmid: 3128610
references.citation: J Immunol Methods. 1999 Feb 1;223(1):77-92
references.pmid: 10037236
references.citation: Br J Pharmacol. 2010 Mar;159(5):1126-32
references.pmid: 20136827
references.citation: Immunology. 1999 Oct;98(2):181-8
references.pmid: 10540216
references.citation: J Immunol. 2001 Jan 15;166(2):1049-56
references.pmid: 11145684
references.citation: Mol Phylogenet Evol. 2009 Aug;52(2):273-83
references.pmid: 19376249
references.citation: J Exp Med. 1992 Dec 1;176(6):1693-702
references.pmid: 1460426
references.citation: J Immunol Methods. 1983 Dec 16;65(1-2):55-63
references.pmid: 6606682
references.citation: Infect Immun. 1986 Jul;53(1):199-206
references.pmid: 2424841
references.citation: Clin Exp Allergy. 1989 May;19(3):255-62
references.pmid: 2660967
references.citation: Braz J Med Biol Res. 2001 Apr;34(4):529-37
references.pmid: 11285466
references.citation: Mycopathologia. 2008 Apr-May;165(4-5):341-52
references.pmid: 18777638
references.citation: J Exp Med. 2003 Aug 18;198(4):615-21
references.pmid: 12925677
references.citation: Mem Inst Oswaldo Cruz. 2009 May;104(3):513-21
references.pmid: 19547881
references.citation: J Biol Chem. 1996 Feb 23;271(8):4553-60
references.pmid: 8626811
references.citation: Nat Rev Immunol. 2002 Mar;2(3):151-61
references.pmid: 11913066
references.citation: Infect Immun. 2006 Apr;74(4):2415-22
references.pmid: 16552071
references.citation: Cancer Res. 1999 Jul 15;59(14):3340-5
references.pmid: 10416590
references.citation: Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15050-5
references.pmid: 10611336
references.citation: Infect Immun. 1998 Feb;66(2):786-93
references.pmid: 9453642
references.citation: Rev Soc Bras Med Trop. 2006 May-Jun;39(3):297-310
references.pmid: 16906260
references.citation: Mycopathologia. 2008 Apr-May;165(4-5):275-87
references.pmid: 18777634
references.citation: Annu Rev Immunol. 2000;18:767-811
references.pmid: 10837075
references.citation: Infect Immun. 1998 Feb;66(2):800-6
references.pmid: 9453644
references.citation: J Med Vet Mycol. 1988;26(6):351-8
references.pmid: 2977619