Crosslinked chitosan microparticles as a safe and efficient DNA carrier for intranasal vaccination against cutaneous leishmaniasis
Intranasal (i.n.) vaccination with adjuvant-free plasmid DNA encoding the leishmanial antigen LACK (LACK DNA) has shown to induce protective immunity against both cutaneous and visceral leishmaniasis in rodents. In the present work, we sought to evaluate the safety and effectiveness of d,l-glycerald...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Vaccine: X |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590136223001444 |
| _version_ | 1797388655970484224 |
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| author | Beatriz L.S. Costa Souza Eduardo F. Pinto Izabella P.S. Bezerra Daniel C.O. Gomes Ana Maria B. Martinez Maria Inês Ré Herbert L. de Matos Guedes Bartira Rossi-Bergmann |
| author_facet | Beatriz L.S. Costa Souza Eduardo F. Pinto Izabella P.S. Bezerra Daniel C.O. Gomes Ana Maria B. Martinez Maria Inês Ré Herbert L. de Matos Guedes Bartira Rossi-Bergmann |
| author_sort | Beatriz L.S. Costa Souza |
| collection | DOAJ |
| description | Intranasal (i.n.) vaccination with adjuvant-free plasmid DNA encoding the leishmanial antigen LACK (LACK DNA) has shown to induce protective immunity against both cutaneous and visceral leishmaniasis in rodents. In the present work, we sought to evaluate the safety and effectiveness of d,l-glyceraldehyde cross-linked chitosan microparticles (CCM) as a LACK DNA non-intumescent mucoadhesive delivery system. CCM with 5 μm of diameter was prepared and adsorbed with a maximum of 2.4 % (w/w) of DNA with no volume alteration. Histological analysis of mouse nostrils instilled with LACK DNA / CCM showed microparticles to be not only mucoadherent but also mucopenetrant, inducing no local inflammation. Systemic safeness was confirmed by the observation that two nasal instillations one week apart did not alter the numbers of bronchoalveolar cells or blood eosinophils; did not alter ALT, AST and creatinine serum levels; and did not induce cutaneous hypersensitivity. When challenged in the footpad with Leishmania amazonensis, mice developed significantly lower parasite loads as compared with animals given naked LACK DNA or CCM alone. That was accompanied by increased stimulation of Th1-biased responses, as seen by the higher T-bet / GATA-3 ratio and IFN-γ levels. Together, these results demonstrate that CCM is a safe and effective mucopenetrating carrier that can increase the efficacy of i.n. LACK DNA vaccination against cutaneous leishmaniasis. |
| first_indexed | 2024-03-08T22:43:58Z |
| format | Article |
| id | doaj.art-1012c43ae1694fbebb4ab8d74a1ea944 |
| institution | Directory Open Access Journal |
| issn | 2590-1362 |
| language | English |
| last_indexed | 2024-03-08T22:43:58Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Vaccine: X |
| spelling | doaj.art-1012c43ae1694fbebb4ab8d74a1ea9442023-12-17T06:41:36ZengElsevierVaccine: X2590-13622023-12-0115100403Crosslinked chitosan microparticles as a safe and efficient DNA carrier for intranasal vaccination against cutaneous leishmaniasisBeatriz L.S. Costa Souza0Eduardo F. Pinto1Izabella P.S. Bezerra2Daniel C.O. Gomes3Ana Maria B. Martinez4Maria Inês Ré5Herbert L. de Matos Guedes6Bartira Rossi-Bergmann7Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, BrazilInstituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, BrazilInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, BrazilNúcleo de Doenças Infecciosas/Núcleo de Biotecnologia, Universidade Federal do Espírito Santo, BrazilLaboratório de Neurodegeneração e Reparo, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, BrazilMines Albi, UMR-CNRS 5302, Centre RAPSODEE, Université de Toulouse, Campus Jarlard, Albi, FranceInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, BrazilInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil; Corresponding author at: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, Av. Carlos Chagas Filho 373, CEP 21941-902 Rio de Janeiro, RJ, Brazil.Intranasal (i.n.) vaccination with adjuvant-free plasmid DNA encoding the leishmanial antigen LACK (LACK DNA) has shown to induce protective immunity against both cutaneous and visceral leishmaniasis in rodents. In the present work, we sought to evaluate the safety and effectiveness of d,l-glyceraldehyde cross-linked chitosan microparticles (CCM) as a LACK DNA non-intumescent mucoadhesive delivery system. CCM with 5 μm of diameter was prepared and adsorbed with a maximum of 2.4 % (w/w) of DNA with no volume alteration. Histological analysis of mouse nostrils instilled with LACK DNA / CCM showed microparticles to be not only mucoadherent but also mucopenetrant, inducing no local inflammation. Systemic safeness was confirmed by the observation that two nasal instillations one week apart did not alter the numbers of bronchoalveolar cells or blood eosinophils; did not alter ALT, AST and creatinine serum levels; and did not induce cutaneous hypersensitivity. When challenged in the footpad with Leishmania amazonensis, mice developed significantly lower parasite loads as compared with animals given naked LACK DNA or CCM alone. That was accompanied by increased stimulation of Th1-biased responses, as seen by the higher T-bet / GATA-3 ratio and IFN-γ levels. Together, these results demonstrate that CCM is a safe and effective mucopenetrating carrier that can increase the efficacy of i.n. LACK DNA vaccination against cutaneous leishmaniasis.http://www.sciencedirect.com/science/article/pii/S2590136223001444Intranasal vaccineDNA-based vaccineVaccine delivery systemsLeishmaniasisChitosan microparticlesGlyceraldehyde crosslinking |
| spellingShingle | Beatriz L.S. Costa Souza Eduardo F. Pinto Izabella P.S. Bezerra Daniel C.O. Gomes Ana Maria B. Martinez Maria Inês Ré Herbert L. de Matos Guedes Bartira Rossi-Bergmann Crosslinked chitosan microparticles as a safe and efficient DNA carrier for intranasal vaccination against cutaneous leishmaniasis Vaccine: X Intranasal vaccine DNA-based vaccine Vaccine delivery systems Leishmaniasis Chitosan microparticles Glyceraldehyde crosslinking |
| title | Crosslinked chitosan microparticles as a safe and efficient DNA carrier for intranasal vaccination against cutaneous leishmaniasis |
| title_full | Crosslinked chitosan microparticles as a safe and efficient DNA carrier for intranasal vaccination against cutaneous leishmaniasis |
| title_fullStr | Crosslinked chitosan microparticles as a safe and efficient DNA carrier for intranasal vaccination against cutaneous leishmaniasis |
| title_full_unstemmed | Crosslinked chitosan microparticles as a safe and efficient DNA carrier for intranasal vaccination against cutaneous leishmaniasis |
| title_short | Crosslinked chitosan microparticles as a safe and efficient DNA carrier for intranasal vaccination against cutaneous leishmaniasis |
| title_sort | crosslinked chitosan microparticles as a safe and efficient dna carrier for intranasal vaccination against cutaneous leishmaniasis |
| topic | Intranasal vaccine DNA-based vaccine Vaccine delivery systems Leishmaniasis Chitosan microparticles Glyceraldehyde crosslinking |
| url | http://www.sciencedirect.com/science/article/pii/S2590136223001444 |
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