A Recombinant Chimeric Protein-Based Vaccine Containing T-Cell Epitopes from Amastigote Proteins and Combined with Distinct Adjuvants, Induces Immunogenicity and Protection against Leishmania infantum Infection

Currently, there is no licensed vaccine to protect against human visceral leishmaniasis (VL), a potentially fatal disease caused by infection with Leishmania parasites. In the current study, a recombinant chimeric protein ChimT was developed based on T-cell epitopes identified from the immunogenic L...

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Autores: Daniela Pagliara Lage, João Augusto Oliveira-da-silva, Fernanda Fonseca Ramos, Grasiele de Sousa Vieira Tavares, Fernanda Ludolf Ribeiro, Raquel S. Bandeira, Isabela A. G. Pereira, Miguel Angel Chaves Fumagalli, Bruno Mendes Roatt, Ricardo A. Machado-de-ávila, Myron Christodoulides, Danniele Luciana Vale, Eduardo Antonio Ferraz Coelho, Vívian Tamietti Martins, Flávia P. Linhares, Camila Simões de Freitas, Amanda Sanchez Machado, Jamile M. O. Cardoso, Daysiane de Oliveira, Nathalia Coral Galvani, Marcelo P. de Oliveira
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:Brasil
Institución:Universidade Federal de Minas Gerais (UFMG)
Repositorio:Repositório Institucional da UFMG
Idioma:inglés
OAI Identifier:oai:repositorio.ufmg.br:1843/60528
Acceso en línea:https://doi.org/10.3390/vaccines10071146
http://hdl.handle.net/1843/60528
https://orcid.org/0000-0001-7882-215X
https://orcid.org/0000-0002-7852-0300
https://orcid.org/0000-0002-8394-4802
https://orcid.org/0000-0002-1303-0490
https://orcid.org/0000-0002-9663-4731
https://orcid.org/0000-0002-6681-9014
Access Level:acceso abierto
Palabra clave:Visceral leishmaniasis
Vaccine
T-cell epitopes
Polypeptide-based protein
Immune response
Adjuvants
Vacinação
Células T.
Peptídeos
Imunidade
Descripción
Sumario:Currently, there is no licensed vaccine to protect against human visceral leishmaniasis (VL), a potentially fatal disease caused by infection with Leishmania parasites. In the current study, a recombinant chimeric protein ChimT was developed based on T-cell epitopes identified from the immunogenic Leishmania amastigote proteins LiHyp1, LiHyV, LiHyC and LiHyG. ChimT was associated with the adjuvants saponin (Sap) or monophosphoryl lipid A (MPLA) and used to immunize mice, and their immunogenicity and protective efficacy were evaluated. Both ChimT/Sap and ChimT/MPLA induced the development of a specific Th1-type immune response, with significantly high levels of IFN-γ, IL-2, IL-12, TNF-α and GM-CSF cytokines produced by CD4+ and CD8+ T cell subtypes (p < 0.05), with correspondingly low production of anti-leishmanial IL-4 and IL-10 cytokines. Significantly increased (p < 0.05) levels of nitrite, a proxy for nitric oxide, and IFN-γ expression (p < 0.05) were detected in stimulated spleen cell cultures from immunized and infected mice, as was significant production of parasite-specific IgG2a isotype antibodies. Significant reductions in the parasite load in the internal organs of the immunized and infected mice (p < 0.05) were quantified with a limiting dilution technique and quantitative PCR and correlated with the immunological findings. ChimT/MPLA showed marginally superior immunogenicity than ChimT/Sap, and although this was not statistically significant (p > 0.05), ChimT/MPLA was preferred since ChimT/Sap induced transient edema in the inoculation site. ChimT also induced high IFN-γ and low IL-10 levels from human PBMCs isolated from healthy individuals and from VL-treated patients. In conclusion, the experimental T-cell multi-epitope amastigote stage Leishmania vaccine administered with adjuvants appears to be a promising vaccine candidate to protect against VL.

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