3 years ago

Recombinant vaccines of a CD4<sup>+</sup> T-cell epitope promote efficient control of <i>Paracoccidioides brasiliensis</i> burden by restraining primary organ infection

Carlos Pelleschi Taborda, Sthefany Pagliari, Lucas Santos Dias, Rodrigo Assunção Holanda, Oscar Bruña-Romero, Julliana Ribeiro Alves Santos, Tatiane Alves Paixão, Julián Esteban Muñoz, Daniel Assis Santos, Érica Leandro Marciano Vieira, Leandro Buffoni Roque Silva

by Rodrigo Assunção Holanda, Julián Esteban Muñoz, Lucas Santos Dias, Leandro Buffoni Roque Silva, Julliana Ribeiro Alves Santos, Sthefany Pagliari, Érica Leandro Marciano Vieira, Tatiane Alves Paixão, Carlos Pelleschi Taborda, Daniel Assis Santos, Oscar Bruña-Romero

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.

Publisher URL: http://journals.plos.org/plosntds/article

DOI: 10.1371/journal.pntd.0005927

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