PMID- 22389734 OWN - NLM STAT- MEDLINE DCOM- 20120622 LR - 20211021 IS - 1935-2735 (Electronic) IS - 1935-2727 (Print) IS - 1935-2727 (Linking) VI - 6 IP - 2 DP - 2012 TI - Therapeutic DNA vaccine encoding peptide P10 against experimental paracoccidioidomycosis. PG - e1519 LID - 10.1371/journal.pntd.0001519 [doi] LID - e1519 AB - Paracoccidioidomycosis (PCM), caused by Paracoccidioides brasiliensis, is the most prevalent invasive fungal disease in South America. Systemic mycoses are the 10th most common cause of death among infectious diseases in Brazil and PCM is responsible for more than 50% of deaths due to fungal infections. PCM is typically treated with sulfonamides, amphotericin B or azoles, although complete eradication of the fungus may not occur and relapsing disease is frequently reported. A 15-mer peptide from the major diagnostic antigen gp43, named P10, can induce a strong T-CD4+ helper-1 immune response in mice. The TEPITOPE algorithm and experimental data have confirmed that most HLA-DR molecules can present P10, which suggests that P10 is a candidate antigen for a PCM vaccine. In the current work, the therapeutic efficacy of plasmid immunization with P10 and/or IL-12 inserts was tested in murine models of PCM. When given prior to or after infection with P. brasiliensis virulent Pb 18 isolate, plasmid-vaccination with P10 and/or IL-12 inserts successfully reduced the fungal burden in lungs of infected mice. In fact, intramuscular administration of a combination of plasmids expressing P10 and IL-12 given weekly for one month, followed by single injections every month for 3 months restored normal lung architecture and eradicated the fungus in mice that were infected one month prior to treatment. The data indicate that immunization with these plasmids is a powerful procedure for prevention and treatment of experimental PCM, with the perspective of being also effective in human patients. FAU - Rittner, Glauce M G AU - Rittner GM AD - Institute of Biomedical Sciences, Department of Microbiology, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil. FAU - Munoz, Julian E AU - Munoz JE FAU - Marques, Alexandre F AU - Marques AF FAU - Nosanchuk, Joshua D AU - Nosanchuk JD FAU - Taborda, Carlos P AU - Taborda CP FAU - Travassos, Luiz R AU - Travassos LR LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120228 PL - United States TA - PLoS Negl Trop Dis JT - PLoS neglected tropical diseases JID - 101291488 RN - 0 (Antigens, Fungal) RN - 0 (Fungal Vaccines) RN - 0 (Glycoproteins) RN - 0 (P10 peptide, Paracoccidioides brasiliensis) RN - 0 (Peptide Fragments) RN - 0 (Vaccines, DNA) SB - IM MH - Animals MH - Antigens, Fungal/*immunology MH - Colony Count, Microbial MH - Disease Models, Animal MH - Fungal Vaccines/administration & dosage/*immunology MH - Genetic Vectors MH - Glycoproteins/*immunology MH - Immunotherapy/*methods MH - Injections, Intramuscular MH - Lung/microbiology/pathology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Paracoccidioides/*immunology MH - Paracoccidioidomycosis/immunology/*therapy MH - Peptide Fragments/*immunology MH - Plasmids MH - Vaccines, DNA/administration & dosage/*immunology PMC - PMC3289603 COIS- The authors have declared that no competing interests exist. EDAT- 2012/03/06 06:00 MHDA- 2012/06/23 06:00 PMCR- 2012/02/28 CRDT- 2012/03/06 06:00 PHST- 2011/04/08 00:00 [received] PHST- 2011/12/23 00:00 [accepted] PHST- 2012/03/06 06:00 [entrez] PHST- 2012/03/06 06:00 [pubmed] PHST- 2012/06/23 06:00 [medline] PHST- 2012/02/28 00:00 [pmc-release] AID - PNTD-D-11-00333 [pii] AID - 10.1371/journal.pntd.0001519 [doi] PST - ppublish SO - PLoS Negl Trop Dis. 2012;6(2):e1519. doi: 10.1371/journal.pntd.0001519. Epub 2012 Feb 28.