PMID- 19204092 OWN - NLM STAT- MEDLINE DCOM- 20090330 LR - 20211020 IS - 1098-5522 (Electronic) IS - 0019-9567 (Print) IS - 0019-9567 (Linking) VI - 77 IP - 4 DP - 2009 Apr TI - Paracoccidioides brasiliensis vaccine formulations based on the gp43-derived P10 sequence and the Salmonella enterica FliC flagellin. PG - 1700-7 LID - 10.1128/IAI.01470-08 [doi] AB - Paracoccidioidomycosis (PCM) is a systemic granulomatous disease caused by the dimorphic fungus Paracoccidioides brasiliensis. Anti-PCM vaccine formulations based on the secreted fungal cell wall protein (gp43) or the derived P10 sequence containing a CD4(+) T-cell-specific epitope have shown promising results. In the present study, we evaluated new anti-PCM vaccine formulations based on the intranasal administration of P. brasiliensis gp43 or the P10 peptide in combination with the Salmonella enterica FliC flagellin, an innate immunity agonist binding specifically to the Toll-like receptor 5, in a murine model. BALB/c mice immunized with gp43 developed high-specific-serum immunoglobulin G1 responses and enhanced interleukin-4 (IL-4) and IL-10 levels. On the other hand, mice immunized with recombinant purified flagellins genetically fused with P10 at the central hypervariable domain, either flanked or not by two lysine residues, or the synthetic P10 peptide admixed with purified FliC elicited a prevailing Th1-type immune response based on lung cell-secreted type 1 cytokines. Mice immunized with gp43 and FliC and intratracheally challenged with P. brasiliensis yeast cells had increased fungal proliferation and lung tissue damage. In contrast, mice immunized with the chimeric flagellins and particularly those immunized with P10 admixed with FliC reduced P. brasiliensis growth and lung damage. Altogether, these results indicate that S. enterica FliC flagellin modulates the immune response to P. brasiliensis P10 antigen and represents a promising alternative for the generation of anti-PCM vaccines. FAU - Braga, Catarina J M AU - Braga CJ AD - Department of Microbiology-ICB, University of Sao Paulo, Av. Prof. Lineu Prestes 1374, Sao Paulo, SP 05008-000, Brazil. FAU - Rittner, Glauce M G AU - Rittner GM FAU - Munoz Henao, Julian E AU - Munoz Henao JE FAU - Teixeira, Aline F AU - Teixeira AF FAU - Massis, Liliana M AU - Massis LM FAU - Sbrogio-Almeida, Maria E AU - Sbrogio-Almeida ME FAU - Taborda, Carlos P AU - Taborda CP FAU - Travassos, Luiz R AU - Travassos LR FAU - Ferreira, Luis C S AU - Ferreira LC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090209 PL - United States TA - Infect Immun JT - Infection and immunity JID - 0246127 RN - 0 (43 kDa protein, Paracoccidioides) RN - 0 (Antibodies, Bacterial) RN - 0 (Antigens, Fungal) RN - 0 (Cytokines) RN - 0 (Fungal Proteins) RN - 0 (Fungal Vaccines) RN - 0 (Glycoproteins) RN - 0 (Peptides) RN - 0 (Recombinant Fusion Proteins) RN - 12777-81-0 (Flagellin) SB - IM MH - Animals MH - Antibodies, Bacterial/blood MH - Antibody Specificity MH - *Antigens, Fungal/chemistry/genetics/immunology MH - Cytokines/metabolism MH - Disease Models, Animal MH - *Flagellin/genetics/immunology/metabolism MH - *Fungal Proteins/chemistry/genetics/immunology MH - *Fungal Vaccines/administration & dosage/genetics/immunology MH - *Glycoproteins/chemistry/genetics/immunology MH - Humans MH - Immunization MH - Lung/immunology/microbiology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Paracoccidioides/*immunology/pathogenicity MH - Paracoccidioidomycosis/immunology/microbiology/*prevention & control MH - *Peptides/chemical synthesis/genetics/immunology MH - Recombinant Fusion Proteins/genetics/immunology/metabolism MH - Salmonella enterica/genetics/immunology/metabolism PMC - PMC2663153 EDAT- 2009/02/11 09:00 MHDA- 2009/03/31 09:00 PMCR- 2009/10/01 CRDT- 2009/02/11 09:00 PHST- 2009/02/11 09:00 [entrez] PHST- 2009/02/11 09:00 [pubmed] PHST- 2009/03/31 09:00 [medline] PHST- 2009/10/01 00:00 [pmc-release] AID - IAI.01470-08 [pii] AID - 1470-08 [pii] AID - 10.1128/IAI.01470-08 [doi] PST - ppublish SO - Infect Immun. 2009 Apr;77(4):1700-7. doi: 10.1128/IAI.01470-08. Epub 2009 Feb 9.