Attempts at a peptide vaccine against paracoccidioidomycosis, adjuvant to chemotherapy

Attempts at a peptide vaccine against paracoccidioidomycosis, adjuvant to chemotherapy

Author Travassos, Luiz Rodolpho Autor UNIFESP Google Scholar
Rodrigues, Elaine Guadalupe Autor UNIFESP Google Scholar
Iwai, Leo Kei Autor UNIFESP Google Scholar
Taborda, Carlos Pelleschi Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Harvard Univ
Universidade de São Paulo (USP)
Abstract Chemotherapy is the basis of treatment of paracoccidioidomycosis in its various forms. Depending on the Paracoccidioides brasiliensis virulence, the status of host immunity, the degree of tissue involvement and fungal dissemination, treatment can be extended for long periods with an alarming frequency of relapses. Association of chemotherapy with a vaccine to boost the cellular immune response seemed a relevant project not only to reduce the time of treatment but also to prevent relapses and improve the prognosis of anergic cases. the candidate immunogen is the gp43 major diagnostic antigen of P. brasiliensis and more specifically its derived peptide P10, carrying the CD4(+) T-cell epitope. Both gp43 and P10 protected Balb/c mice against intratracheal infections with virulent P. brasiliensis strain. P10 as single peptide or in a multiple-antigen-peptide (MAP) tetravalent construction was protective without adjuvant either by preimmunization and intratracheal challenge or as a therapeutic agent in mice with installed infection. P10 showed additive protective effects in drug-treated mice stimulating a Th-1 type immune response with high IFN-gamma and IL-12. P10 and few other peptides in the gp43 were selected by Tepitope algorithm and actually shown to promiscuously bind several prominent HLA-DR molecules suggesting that a peptide vaccine could be devised for a genetically heterogenous population. P10 was protective in animals turned anergic, was effective in a DNA minigene vaccine, and increased the protection by monoclonal antibodies in Balb/c mice. DNA vaccines and peptide vaccines are promising therapeutic tools to be explored in the control of systemic mycoses.
Keywords paracoccidioidomycosis
Paracoccidioides brasiliensis
peptide vaccine
Language English
Date 2008-04-01
Published in Mycopathologia. Dordrecht: Springer, v. 165, n. 4-5, p. 341-352, 2008.
ISSN 0301-486X (Sherpa/Romeo, impact factor)
Publisher Springer
Extent 341-352
Access rights Closed access
Type Article
Web of Science ID WOS:000255256100014

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