Therapeutic Vaccination with Cationic Liposomes Formulated with Dioctadecyldimethylammonium and Trehalose Dibehenate (CAF01) and Peptide P10 Is Protective in Mice Infected with <i>Paracoccidioides brasiliensis</i>
The peptide P10 is a vaccine candidate for Paracoccidioidomycosis, a systemic mycosis caused by fungal species of the genus <i>Paracoccidioides</i> spp. We have previously shown that peptide P10 vaccination, in the presence of several different adjuvants, induced a protective cellular im...
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| Format: | Article |
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MDPI AG
2020-12-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/6/4/347 |
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| author | Marcelo Valdemir de Araújo Samuel Rodrigues Dos Santos Júnior Joshua D. Nosanchuk Carlos Pelleschi Taborda |
| author_facet | Marcelo Valdemir de Araújo Samuel Rodrigues Dos Santos Júnior Joshua D. Nosanchuk Carlos Pelleschi Taborda |
| author_sort | Marcelo Valdemir de Araújo |
| collection | DOAJ |
| description | The peptide P10 is a vaccine candidate for Paracoccidioidomycosis, a systemic mycosis caused by fungal species of the genus <i>Paracoccidioides</i> 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<sup>+</sup> Th<sub>1</sub> lymphocytes that was associated with the increased production of IFN-γ in mice challenged with a virulent isolate of <i>Paracoccidoides brasiliensis</i>. 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<sub>1</sub>/Th<sub>17</sub> 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 <i>P. brasiliensis</i>. 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 µg/mL and 20 µg of P10 induced an effective cellular immune response with increased levels of Th<sub>17</sub> 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 µg/mL with 20 µg of P10 are a promising therapeutic for safely and effectively improving the treatment of paracoccidioidomycosis. |
| first_indexed | 2024-03-10T14:15:51Z |
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| language | English |
| last_indexed | 2024-03-10T14:15:51Z |
| publishDate | 2020-12-01 |
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| spelling | doaj.art-b3da62bce00847ef943a42729cdd80842023-11-20T23:51:02ZengMDPI AGJournal of Fungi2309-608X2020-12-016434710.3390/jof6040347Therapeutic Vaccination with Cationic Liposomes Formulated with Dioctadecyldimethylammonium and Trehalose Dibehenate (CAF01) and Peptide P10 Is Protective in Mice Infected with <i>Paracoccidioides brasiliensis</i>Marcelo Valdemir de Araújo0Samuel Rodrigues Dos Santos Júnior1Joshua D. Nosanchuk2Carlos Pelleschi Taborda3Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo 05508-000, BrazilDepartamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo 05508-000, BrazilDepartments of Medicine (Division of Infectious Disease), Microbiology and Immunology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY 10461, USADepartamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo 05508-000, BrazilThe peptide P10 is a vaccine candidate for Paracoccidioidomycosis, a systemic mycosis caused by fungal species of the genus <i>Paracoccidioides</i> 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<sup>+</sup> Th<sub>1</sub> lymphocytes that was associated with the increased production of IFN-γ in mice challenged with a virulent isolate of <i>Paracoccidoides brasiliensis</i>. 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<sub>1</sub>/Th<sub>17</sub> 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 <i>P. brasiliensis</i>. 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 µg/mL and 20 µg of P10 induced an effective cellular immune response with increased levels of Th<sub>17</sub> 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 µg/mL with 20 µg of P10 are a promising therapeutic for safely and effectively improving the treatment of paracoccidioidomycosis.https://www.mdpi.com/2309-608X/6/4/347paracoccidioidomycosis<i>P. brasiliensis</i>peptide vaccineadjuvantCAF01DDA/TDB |
| spellingShingle | Marcelo Valdemir de Araújo Samuel Rodrigues Dos Santos Júnior Joshua D. Nosanchuk Carlos Pelleschi Taborda Therapeutic Vaccination with Cationic Liposomes Formulated with Dioctadecyldimethylammonium and Trehalose Dibehenate (CAF01) and Peptide P10 Is Protective in Mice Infected with <i>Paracoccidioides brasiliensis</i> Journal of Fungi paracoccidioidomycosis <i>P. brasiliensis</i> peptide vaccine adjuvant CAF01 DDA/TDB |
| title | Therapeutic Vaccination with Cationic Liposomes Formulated with Dioctadecyldimethylammonium and Trehalose Dibehenate (CAF01) and Peptide P10 Is Protective in Mice Infected with <i>Paracoccidioides brasiliensis</i> |
| title_full | Therapeutic Vaccination with Cationic Liposomes Formulated with Dioctadecyldimethylammonium and Trehalose Dibehenate (CAF01) and Peptide P10 Is Protective in Mice Infected with <i>Paracoccidioides brasiliensis</i> |
| title_fullStr | Therapeutic Vaccination with Cationic Liposomes Formulated with Dioctadecyldimethylammonium and Trehalose Dibehenate (CAF01) and Peptide P10 Is Protective in Mice Infected with <i>Paracoccidioides brasiliensis</i> |
| title_full_unstemmed | Therapeutic Vaccination with Cationic Liposomes Formulated with Dioctadecyldimethylammonium and Trehalose Dibehenate (CAF01) and Peptide P10 Is Protective in Mice Infected with <i>Paracoccidioides brasiliensis</i> |
| title_short | Therapeutic Vaccination with Cationic Liposomes Formulated with Dioctadecyldimethylammonium and Trehalose Dibehenate (CAF01) and Peptide P10 Is Protective in Mice Infected with <i>Paracoccidioides brasiliensis</i> |
| title_sort | therapeutic vaccination with cationic liposomes formulated with dioctadecyldimethylammonium and trehalose dibehenate caf01 and peptide p10 is protective in mice infected with i paracoccidioides brasiliensis i |
| topic | paracoccidioidomycosis <i>P. brasiliensis</i> peptide vaccine adjuvant CAF01 DDA/TDB |
| url | https://www.mdpi.com/2309-608X/6/4/347 |
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