PMID- 28938005 OWN - NLM STAT- MEDLINE DCOM- 20171025 LR - 20181202 IS - 1935-2735 (Electronic) IS - 1935-2727 (Print) IS - 1935-2727 (Linking) VI - 11 IP - 9 DP - 2017 Sep TI - Recombinant vaccines of a CD4+ T-cell epitope promote efficient control of Paracoccidioides brasiliensis burden by restraining primary organ infection. PG - e0005927 LID - 10.1371/journal.pntd.0005927 [doi] LID - e0005927 AB - 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. FAU - Holanda, Rodrigo Assuncao AU - Holanda RA AUID- ORCID: 0000-0002-1698-5663 AD - Departamento de Microbiologia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil. AD - Laboratorio de Biologia Parasitaria, Universidade CEUMA, Maranhao, Brazil. FAU - Munoz, Julian Esteban AU - Munoz JE AD - Departamento de Microbiologia, Universidade de Sao Paulo, Sao Paulo, Brazil. AD - Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogota, Colombia. FAU - Dias, Lucas Santos AU - Dias LS AD - Departamento de Microbiologia, Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Silva, Leandro Buffoni Roque AU - Silva LBR AD - Departamento de Microbiologia, Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Santos, Julliana Ribeiro Alves AU - Santos JRA AD - Departamento de Microbiologia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil. AD - Laboratorio de Microbiologia Ambiental, Universidade CEUMA, Maranhao, Brazil. FAU - Pagliari, Sthefany AU - Pagliari S AD - Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Santa Catarina, Brazil. FAU - Vieira, Erica Leandro Marciano AU - Vieira ELM AD - Faculdade de Medicina, Universidade Federal de Minas Gerais, Minas Gerais, Brazil. FAU - Paixao, Tatiane Alves AU - Paixao TA AD - Departamento de Patologia Geral, Universidade Federal de Minas Gerais, Minas Gerais, Brazil. FAU - Taborda, Carlos Pelleschi AU - Taborda CP AD - Departamento de Microbiologia, Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Santos, Daniel Assis AU - Santos DA AD - Departamento de Microbiologia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil. FAU - Bruna-Romero, Oscar AU - Bruna-Romero O AD - Departamento de Microbiologia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil. AD - Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Santa Catarina, Brazil. LA - eng PT - Journal Article DEP - 20170922 PL - United States TA - PLoS Negl Trop Dis JT - PLoS neglected tropical diseases JID - 101291488 RN - 0 (43 kDa protein, Paracoccidioides) RN - 0 (Antigens, Fungal) RN - 0 (Cytokines) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (Fungal Proteins) RN - 0 (Fungal Vaccines) RN - 0 (Glycoproteins) RN - 0 (Immunodominant Epitopes) RN - 0 (Vaccines, Synthetic) RN - 0 (Vaccines, Virus-Like Particle) SB - IM MH - Animals MH - Antigens, Fungal/*immunology MH - CD4-Positive T-Lymphocytes/*immunology MH - Cytokines/immunology/metabolism MH - Epitopes, T-Lymphocyte/genetics/*immunology MH - Fungal Proteins/*immunology MH - Fungal Vaccines/*administration & dosage/immunology MH - Glycoproteins/*immunology MH - Hepatitis B virus/genetics MH - Immunization MH - Immunodominant Epitopes/immunology MH - Immunogenicity, Vaccine MH - Immunologic Memory MH - Liver/microbiology MH - Lung/microbiology MH - Mice, Inbred BALB C MH - Paracoccidioides/*growth & development/*immunology MH - Paracoccidioidomycosis/immunology/microbiology/*prevention & control MH - Spleen/microbiology MH - Th1 Cells/immunology MH - Vaccines, Synthetic/administration & dosage/genetics/immunology MH - Vaccines, Virus-Like Particle/administration & dosage/genetics/immunology PMC - PMC5627964 COIS- I have read the journal's policy and the authors of this manuscript have the following competing interests: RAH, DAS, CPT and OBR are inventors on patent application [BR1020150311150] of the recombinant vaccines that was assigned by National Institute of Industrial Property, Brazil. EDAT- 2017/09/25 06:00 MHDA- 2017/10/27 06:00 PMCR- 2017/09/22 CRDT- 2017/09/23 06:00 PHST- 2017/03/08 00:00 [received] PHST- 2017/09/02 00:00 [accepted] PHST- 2017/10/04 00:00 [revised] PHST- 2017/09/25 06:00 [pubmed] PHST- 2017/10/27 06:00 [medline] PHST- 2017/09/23 06:00 [entrez] PHST- 2017/09/22 00:00 [pmc-release] AID - PNTD-D-17-00330 [pii] AID - 10.1371/journal.pntd.0005927 [doi] PST - epublish SO - PLoS Negl Trop Dis. 2017 Sep 22;11(9):e0005927. doi: 10.1371/journal.pntd.0005927. eCollection 2017 Sep.