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Recombinant vaccines of a CD4+ T-cell epitope promote efficient control of Paracoccidioides brasiliensis burden by restraining primary organ infection
Authors
Tatiane Alves Paixão
Julliana Ribeiro Alves Santos
+11 more
Julliana Ribeiro Alves Santos
Daniel Assis Santos
Rodrigo Assuncão Holanda
Oscar Bruña-Romero
Érica Leandro
Julián Esteban Muñoz Henao
Sthefany Pagliari
Carlos Pelleschi Taborda
Leandro Buffoni Roque Silva
Lucas Santos Dias
Marciano Vieira
Publication date
6 November 2018
Publisher
Doi
Cite
Abstract
Paracoccidioidomycosis (PCM) is an infectious disease endemic to South America, caused by the thermally dimorphic fungi Paracoccidioides. Currently, there is no effective human vaccine that can be used in prophylactic or therapeutic regimes. We tested the hypothesis that the immunogenicity of the immunodominant CD4+T-cell epitope (P10) of Paracoccidioides brasiliensis gp43 antigen might be significantly enhanced by using a hepatitis B virus-derived particle (VLP) as an antigen carrier. This chimera was administered to mice as a (His)6-purified protein (rPbT) or a replication-deficient human type 5 adenoviral vector (rAdPbT) in an immunoprophylaxis assay. The highly virulent Pb18 yeast strain was used to challenge our vaccine candidates. Fungal challenge evoked robust P10-specific memory CD4+T cells secreting protective Th-1 cytokines in most groups of immunized mice. Furthermore, the highest level of fungal burden control was achieved when rAdPbT was inoculated in a homologous prime-boost regimen, with 10-fold less CFU recovering than in non-vaccinated mice. Systemic Pb18 spreading was only prevented when rAdPbT was previously inoculated. In summary, we present here VLP/P10 formulations as vaccine candidates against PCM, some of which have demonstrated for the first time their ability to prevent progression of this pernicious fungal disease, which represents a significant social burden in developing countries. © 2017 Holanda et al
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LAReferencia - Red Federada de Repositorios Institucionales de Publicaciones Científicas Latinoamericanas
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Last time updated on 26/12/2021