Therapeutic DNA vaccine encoding peptide P10 against experimental paracoccidioidomycosis

Glauce M G Rittner, Julián E. Muñoz, Alexandre F. Marques, Joshua D. Nosanchuk, Carlos P. Taborda, Luiz R. Travassos

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere1519
JournalPLoS Neglected Tropical Diseases
Volume6
Issue number2
DOIs
StatePublished - Feb 2012

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Paracoccidioidomycosis
DNA Vaccines
Peptides
Mycoses
Plasmids
Interleukin-12
Paracoccidioides
Immunization
Fungi
Therapeutics
Azoles
Lung
South America
Sulfonamides
Amphotericin B
HLA-DR Antigens
Communicable Diseases
Brazil
Cause of Death
Vaccination

ASJC Scopus subject areas

  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Therapeutic DNA vaccine encoding peptide P10 against experimental paracoccidioidomycosis. / Rittner, Glauce M G; Muñoz, Julián E.; Marques, Alexandre F.; Nosanchuk, Joshua D.; Taborda, Carlos P.; Travassos, Luiz R.

In: PLoS Neglected Tropical Diseases, Vol. 6, No. 2, e1519, 02.2012.

Research output: Contribution to journalArticle

Rittner, Glauce M G ; Muñoz, Julián E. ; Marques, Alexandre F. ; Nosanchuk, Joshua D. ; Taborda, Carlos P. ; Travassos, Luiz R. / Therapeutic DNA vaccine encoding peptide P10 against experimental paracoccidioidomycosis. In: PLoS Neglected Tropical Diseases. 2012 ; Vol. 6, No. 2.
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