Therapeutic DNA Vaccine Encoding Peptide P10 against Experimental Paracoccidioidomycosis

Author(s)

Rittner, Glauce M. G. ^[1] ; Munoz, Julian E. ^[1] ; Marques, Alexandre F. ^[1] ; Nosanchuk, Joshua D. ^{[2, 3]} ; Taborda, Carlos P. ^{[1, 4]} ; Travassos, Luiz R. ^[5]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo - Brazil

^[2] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 - USA

^[3] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 - USA

^[4] Univ Sao Paulo, Med Mycol Lab IMTSP & HCFMUSP LIM53, Sao Paulo - Brazil

^[5] Fed Univ Sao Paulo UNIFESP, Div Cell Biol, Dept Microbiol Immunol & Parasitol, Sao Paulo - Brazil

• Document type: Journal article
• Source: PLoS Neglected Tropical Diseases; v. 6, n. 2, p. e1519, 2012.
• Web of Science Citations: 25

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. (AU)

• FAPESP's process: 06/50634-2 - Peptides and peptidases: biological activities in infectious diseases and cancer
• Grantee: Luiz Rodolpho Raja Gabaglia Travassos
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 07/07588-2 - Efficacy and biological function of monoclonal antibodies against cell wall and exoantigens from Paracoccidioides brasiliensis
• Grantee: Carlos Pelleschi Taborda
• Support Opportunities: Regular Research Grants
• FAPESP's process: 09/15823-7 - Use of dendritic cells from mice and human pulsed with pVAX vector containing insert for the expression of P10 or P10 synthetic peptide derived from the GP 43 of P. brasiliensis, as vaccine strategy against paracoccidioidomycosis
• Grantee: Carlos Pelleschi Taborda
• Support Opportunities: Regular Research Grants