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Immunization with recombinant LiHyp1 protein plus adjuvant is protective against tegumentary leishmaniasis

Immunization with recombinant LiHyp1 protein plus adjuvant is protective against tegumentary leishmaniasis
Immunization with recombinant LiHyp1 protein plus adjuvant is protective against tegumentary leishmaniasis
Tegumentary leishmaniasis (TL) is the main clinical manifestation of leishmaniasis, and it can cause the infected hosts to self-healing cutaneous lesions until mutilating scars in mucosal membranes, particularly in the nose and throat. The treatment against disease presents problems, and the diagnosis is hampered by variable sensitivity and/or specificity of the tests. In this context, the development of prophylactic vaccines could be considered as a strategy to control the disease. Previously, we showed that the recombinant LiHyp1 protein plus adjuvant protected mice from infection with Leishmania infantum, which causes visceral leishmaniasis. In the present study, we tested whether rLiHyp1 could induce protection against infection with L. amazonensis, a parasite species able to cause TL. We immunized BALB/c mice with rLiHyp1 plus saponin (rLiHyp1/S) or incorporated in micelles (rLiHyp1/M) as adjuvants and performed parasitological and immunological evaluations before and after infection. Results showed that after in vitro stimulation from spleen cell cultures using rLiHyp1 or a Leishmania antigenic extract (SLA), rLiHyp1/S and rLiHyp1/M groups developed a Th1-type immune response, which was characterized by high levels of IFN-γ, IL-2, TNF-α and IL-12 cytokines, nitrite, and IgG2a isotype antibodies when compared to values found in the control (saline, saponin, micelles alone) groups, which showed higher levels of anti-SLA IL-4, IL-10, and IgG1 antibodies before and after challenge. In addition, mice receiving rLiHyp1/S or rLiHyp1/M presented significant reductions in the lesion average diameter and parasite load in the infected tissue and internal organs. Blood samples were collected from healthy subjects and TL patients to obtain PBMC cultures, which were in vitro stimulated with rLiHyp1 or SLA, and results showed higher lymphoproliferation and IFN-γ production after stimulus using rLiHyp1, as compared to values found using SLA. These results suggest that rLiHyp1 plus adjuvant was protective against experimental TL and could also be considered for future studies as a vaccine candidate against human disease.
PBMC, Polymeric micelles, Saponin, Tegumentary leishmaniasis, Vaccine, rLiHyp1
0932-0113
2917-2931
Jesus, Marcelo M.
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Lage, Daniela P.
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Vale, Danniele L.
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Freitas, Camila S.
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Pimenta, Breno L.
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Moreira, Gabriel J.L.
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Ramos, Fernanda F.
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Pereira, Isabela A.G.
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Bandeira, Raquel S.
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Ludolf, Fernanda
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Tavares, Grasiele S.V.
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Galdino, Alexsandro S.
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Duarte, Mariana C.
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Menezes-Souza, Daniel
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Chávez-Fumagalli, Miguel A.
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Teixeira, Antônio L.
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Gonçalves, Denise U.
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Roatt, Bruno M.
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Christodoulides, Myron
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Martins, Vívian T.
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Coelho, Eduardo A.F.
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Jesus, Marcelo M.
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Lage, Daniela P.
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Vale, Danniele L.
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Freitas, Camila S.
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Pimenta, Breno L.
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Moreira, Gabriel J.L.
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Ramos, Fernanda F.
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Pereira, Isabela A.G.
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Bandeira, Raquel S.
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Ludolf, Fernanda
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Tavares, Grasiele S.V.
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Galdino, Alexsandro S.
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Duarte, Mariana C.
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Menezes-Souza, Daniel
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Chávez-Fumagalli, Miguel A.
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Teixeira, Antônio L.
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Gonçalves, Denise U.
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Roatt, Bruno M.
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Christodoulides, Myron
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Martins, Vívian T.
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Coelho, Eduardo A.F.
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Jesus, Marcelo M., Lage, Daniela P., Vale, Danniele L., Freitas, Camila S., Pimenta, Breno L., Moreira, Gabriel J.L., Ramos, Fernanda F., Pereira, Isabela A.G., Bandeira, Raquel S., Ludolf, Fernanda, Tavares, Grasiele S.V., Galdino, Alexsandro S., Duarte, Mariana C., Menezes-Souza, Daniel, Chávez-Fumagalli, Miguel A., Teixeira, Antônio L., Gonçalves, Denise U., Roatt, Bruno M., Christodoulides, Myron, Martins, Vívian T. and Coelho, Eduardo A.F. (2023) Immunization with recombinant LiHyp1 protein plus adjuvant is protective against tegumentary leishmaniasis. Parasitology Research, 122 (12), 2917-2931. (doi:10.1007/s00436-023-07981-6).

Record type: Article

Abstract

Tegumentary leishmaniasis (TL) is the main clinical manifestation of leishmaniasis, and it can cause the infected hosts to self-healing cutaneous lesions until mutilating scars in mucosal membranes, particularly in the nose and throat. The treatment against disease presents problems, and the diagnosis is hampered by variable sensitivity and/or specificity of the tests. In this context, the development of prophylactic vaccines could be considered as a strategy to control the disease. Previously, we showed that the recombinant LiHyp1 protein plus adjuvant protected mice from infection with Leishmania infantum, which causes visceral leishmaniasis. In the present study, we tested whether rLiHyp1 could induce protection against infection with L. amazonensis, a parasite species able to cause TL. We immunized BALB/c mice with rLiHyp1 plus saponin (rLiHyp1/S) or incorporated in micelles (rLiHyp1/M) as adjuvants and performed parasitological and immunological evaluations before and after infection. Results showed that after in vitro stimulation from spleen cell cultures using rLiHyp1 or a Leishmania antigenic extract (SLA), rLiHyp1/S and rLiHyp1/M groups developed a Th1-type immune response, which was characterized by high levels of IFN-γ, IL-2, TNF-α and IL-12 cytokines, nitrite, and IgG2a isotype antibodies when compared to values found in the control (saline, saponin, micelles alone) groups, which showed higher levels of anti-SLA IL-4, IL-10, and IgG1 antibodies before and after challenge. In addition, mice receiving rLiHyp1/S or rLiHyp1/M presented significant reductions in the lesion average diameter and parasite load in the infected tissue and internal organs. Blood samples were collected from healthy subjects and TL patients to obtain PBMC cultures, which were in vitro stimulated with rLiHyp1 or SLA, and results showed higher lymphoproliferation and IFN-γ production after stimulus using rLiHyp1, as compared to values found using SLA. These results suggest that rLiHyp1 plus adjuvant was protective against experimental TL and could also be considered for future studies as a vaccine candidate against human disease.

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e-pub ahead of print date: 28 September 2023
Published date: December 2023
Additional Information: Funding Information: The study was supported by grant APQ-02167-21 from the Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), Brazil. The authors also thank the Brazilian agencies Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), FAPEMIG, and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for student scholarships. Publisher Copyright: © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Keywords: PBMC, Polymeric micelles, Saponin, Tegumentary leishmaniasis, Vaccine, rLiHyp1

Identifiers

Local EPrints ID: 485882
URI: http://eprints.soton.ac.uk/id/eprint/485882
ISSN: 0932-0113
PURE UUID: 045fc111-4a91-4b57-b53b-53419b3c603b
ORCID for Myron Christodoulides: ORCID iD orcid.org/0000-0002-9663-4731

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Date deposited: 03 Jan 2024 19:34
Last modified: 01 Oct 2024 04:01

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Contributors

Author: Marcelo M. Jesus
Author: Daniela P. Lage
Author: Danniele L. Vale
Author: Camila S. Freitas
Author: Breno L. Pimenta
Author: Gabriel J.L. Moreira
Author: Fernanda F. Ramos
Author: Isabela A.G. Pereira
Author: Raquel S. Bandeira
Author: Fernanda Ludolf
Author: Grasiele S.V. Tavares
Author: Alexsandro S. Galdino
Author: Mariana C. Duarte
Author: Daniel Menezes-Souza
Author: Miguel A. Chávez-Fumagalli
Author: Antônio L. Teixeira
Author: Denise U. Gonçalves
Author: Bruno M. Roatt
Author: Vívian T. Martins
Author: Eduardo A.F. Coelho

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