Paracoccidioides brasiliensis Vaccine Formulations Based on the gp43-Derived P10 Sequence and the Salmonella enterica FliC Flagellin

Paracoccidioides brasiliensis Vaccine Formulations Based on the gp43-Derived P10 Sequence and the Salmonella enterica FliC Flagellin

Author Braga, Catarina J. M. Google Scholar
Rittner, Glauce M. G. Google Scholar
Munoz Henao, Julian E. Google Scholar
Teixeira, Aline F. Google Scholar
Massis, Liliana M. Google Scholar
Sbrogio-Almeida, Maria E. Google Scholar
Taborda, Carlos Pelleschi Autor UNIFESP Google Scholar
Travassos, Luiz R. Autor UNIFESP Google Scholar
Ferreira, Luis C. S. Google Scholar
Institution Universidade de São Paulo (USP)
Inst Butantan
Universidade Federal de São Paulo (UNIFESP)
Abstract 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.
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Date 2009-04-01
Published in Infection and Immunity. Washington: Amer Soc Microbiology, v. 77, n. 4, p. 1700-1707, 2009.
ISSN 0019-9567 (Sherpa/Romeo, impact factor)
Publisher Amer Soc Microbiology
Extent 1700-1707
Origin http://dx.doi.org/10.1128/IAI.01470-08
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000264191500045
URI http://repositorio.unifesp.br/handle/11600/31401

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