Back to Search
Start Over
Recombinant vaccines of a CD4+ T-cell epitope promote efficient control of Paracoccidioides brasiliensis burden by restraining primary organ infection.
- Source :
-
PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2017 Sep 22; Vol. 11 (9), pp. e0005927. Date of Electronic Publication: 2017 Sep 22 (Print Publication: 2017). - Publication Year :
- 2017
-
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.
- Subjects :
- Animals
Cytokines immunology
Cytokines metabolism
Epitopes, T-Lymphocyte genetics
Fungal Vaccines immunology
Hepatitis B virus genetics
Immunization
Immunodominant Epitopes immunology
Immunogenicity, Vaccine
Immunologic Memory
Liver microbiology
Lung microbiology
Mice, Inbred BALB C
Paracoccidioidomycosis immunology
Paracoccidioidomycosis microbiology
Spleen microbiology
Th1 Cells immunology
Vaccines, Synthetic administration & dosage
Vaccines, Synthetic genetics
Vaccines, Synthetic immunology
Vaccines, Virus-Like Particle administration & dosage
Vaccines, Virus-Like Particle genetics
Vaccines, Virus-Like Particle immunology
Antigens, Fungal immunology
CD4-Positive T-Lymphocytes immunology
Epitopes, T-Lymphocyte immunology
Fungal Proteins immunology
Fungal Vaccines administration & dosage
Glycoproteins immunology
Paracoccidioides growth & development
Paracoccidioides immunology
Paracoccidioidomycosis prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1935-2735
- Volume :
- 11
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- PLoS neglected tropical diseases
- Publication Type :
- Academic Journal
- Accession number :
- 28938005
- Full Text :
- https://doi.org/10.1371/journal.pntd.0005927