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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Therapeutic Vaccination with Cationic Liposomes Formulated with Dioctadecyldimethylammonium and Trehalose Dibehenate (CAF01) and Peptide P10 Is Protective in Mice Infected with Paracoccidioides brasiliensis

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Author(s):
de Araujo, Marcelo Valdemir [1] ; Dos Santos Junior, Samuel Rodrigues [1] ; Nosanchuk, Joshua D. [2, 3, 4, 5] ; Taborda, Carlos Pelleschi [1, 6]
Total Authors: 4
Affiliation:
[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, BR-05508000 Sao Paulo - Brazil
[2] Albert Einstein Coll Med, Dept Med, Div Infect Dis, Bronx, NY 10461 - USA
[3] Albert Einstein Coll Med, Dept Microbiol, Div Infect Dis, Bronx, NY 10461 - USA
[4] Albert Einstein Coll Med, Dept Immunol, Div Infect Dis, Bronx, NY 10461 - USA
[5] Montefiore Med Ctr, Bronx, NY 10461 - USA
[6] Univ Sao Paulo, Fac Med, Inst Med Trop Sao Paulo LIM53, Dept Dermatol, BR-4023062 Sao Paulo - Brazil
Total Affiliations: 6
Document type: Journal article
Source: JOURNAL OF FUNGI; v. 6, n. 4 DEC 2020.
Web of Science Citations: 0
Abstract

The peptide P10 is a vaccine candidate for Paracoccidioidomycosis, a systemic mycosis caused by fungal species of the genus Paracoccidioides spp. We have previously shown that peptide P10 vaccination, in the presence of several different adjuvants, induced a protective cellular immune response mediated by CD4(+) Th-1 lymphocytes that was associated with the increased production of IFN-gamma in mice challenged with a virulent isolate of Paracoccidoides brasiliensis. Cationic liposomes formulated with dioctadecyldimethylammonium and trehalose dibehenate (DDA/TDB, termed also CAF01-cationic adjuvant formulation) have been developed for safe administration in humans and CAF01 liposomes are utilized as an adjuvant for modulating a robust Th-1/Th-17 cellular response. We evaluated the efficacy of the adsorption of peptide P10 to CAF01 cationic liposomes and used the generated liposomes to vaccinate C57Bl/6 mice infected with P. brasiliensis. Our results showed that P10 was efficiently adsorbed onto CAF01 liposomes. The vaccination of infected mice with cationic liposomes formulated with DDA/TDB 250/50 mu g/mL and 20 mu g of P10 induced an effective cellular immune response with increased levels of Th-17 cytokines, which correlated with significant decreases in the fungal burdens in lungs and protective granulomatous tissue responses. Hence, cationic liposomes of DDA/TDB 250/50 mu g/mL with 20 mu g of P10 are a promising therapeutic for safely and effectively improving the treatment of paracoccidioidomycosis. (AU)

FAPESP's process: 16/08730-6 - Fungal pathogenicity: environmental effects, immune response and vaccine modulation in the Brazilian endemic mycoses paracoccidioidomycosis and histoplasmosis
Grantee:Carlos Pelleschi Taborda
Support Opportunities: Research Projects - Thematic Grants