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Leishmania eukaryotic elongation Factor-1 beta protein is immunogenic and induces parasitological protection in mice against Leishmania infantum infection

Leishmania eukaryotic elongation Factor-1 beta protein is immunogenic and induces parasitological protection in mice against Leishmania infantum infection
Leishmania eukaryotic elongation Factor-1 beta protein is immunogenic and induces parasitological protection in mice against Leishmania infantum infection
Treatment for visceral leishmaniasis (VL) is hampered mainly by the toxicity and/or high cost of antileishmanial drugs. What is more, variability on sensitivity and/or specificity of diagnostic tests hinders effective disease management. In this context, prophylactic vaccination should be considered as a strategy to prevent disease. In the present study, immunogenicity of the Leishmania eukaryotic Elongation Factor-1 beta (EF1b) protein, classified as a Leishmania virulence factor, was evaluated in vitro and in vivo and tested, for the first time, as a vaccine candidate against Leishmania infantum infection. The antigen was administered as DNA vaccine or as recombinant protein (rEF1b) delivered in saponin. BALB/c mice immunization with a DNA plasmid and recombinant protein plus saponin induced development of specific Th1-type immunity, characterized by high levels of IFN-γ, IL-12, GM-CSF, both T cell subtypes and antileishmanial IgG2a isotype antibodies, before and after infection. This immunological response to the vaccines was corroborated further by parasitological analysis of the vaccinated and then challenged mice, which showed significant reductions in the parasite load in their liver, spleen, bone marrow and draining lymph nodes, when compared to the controls. Vaccination using rEF1b/saponin induced a more robust Th1 response and parasitological protection when compared to the DNA vaccine. Furthermore, in vitro analysis of lymphoproliferation, IFN-γ and IL-10 levels in human PBMC cultures showed as well development of a specific Th1-type response. In conclusion, data suggest that EF1b could be a promising vaccine candidate to protect against L. infantum infection.
DNA vaccine, Eukaryotic elongation Factor-1 beta, Leishmania infantum, Recombinant protein, Vaccine, Visceral leishmaniasis
0882-4010
Santos, Thais T.O.
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Sanchez Machado, Amanda
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Fonseca Ramos, Fernanda
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Oliveira-da-Silva, Joao A
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Lage, Daniela P
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Tavares, Grasiele S.V.
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Mendoca, Debora V.C.
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Cardoso, Mariana S
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Siqueira, Williane F
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Martins, Vivian T
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Ludolf, Fernanda
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Reis, Thiago A.R.
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Carvalho, Livia M.
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Freitas, Camila S.
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Bandeira, Raquel S
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Silva, Alessandra M
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Oliveira, Jamil S.
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Moreira, Ricardo L F
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Fujiwara, Ricardo T
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Roatt, Bruno M.
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Chavez-Fumigalli, Miguel A
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Humbert, Maria V
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Teixeira, Antonio L.
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Ferraz Coelho, Eduardo Antonio
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Santos, Thais T.O.
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Sanchez Machado, Amanda
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Fonseca Ramos, Fernanda
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Oliveira-da-Silva, Joao A
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Lage, Daniela P
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Tavares, Grasiele S.V.
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Mendoca, Debora V.C.
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Cardoso, Mariana S
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Siqueira, Williane F
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Martins, Vivian T
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Ludolf, Fernanda
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Reis, Thiago A.R.
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Carvalho, Livia M.
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Freitas, Camila S.
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Bandeira, Raquel S
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Silva, Alessandra M
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Oliveira, Jamil S.
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Moreira, Ricardo L F
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Fujiwara, Ricardo T
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Roatt, Bruno M.
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Chavez-Fumigalli, Miguel A
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Humbert, Maria V
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Teixeira, Antonio L.
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Ferraz Coelho, Eduardo Antonio
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Santos, Thais T.O., Sanchez Machado, Amanda, Fonseca Ramos, Fernanda, Oliveira-da-Silva, Joao A, Lage, Daniela P, Tavares, Grasiele S.V., Mendoca, Debora V.C., Cardoso, Mariana S, Siqueira, Williane F, Martins, Vivian T, Ludolf, Fernanda, Reis, Thiago A.R., Carvalho, Livia M., Freitas, Camila S., Bandeira, Raquel S, Silva, Alessandra M, Oliveira, Jamil S., Moreira, Ricardo L F, Fujiwara, Ricardo T, Roatt, Bruno M., Chavez-Fumigalli, Miguel A, Humbert, Maria V, Teixeira, Antonio L. and Ferraz Coelho, Eduardo Antonio (2021) Leishmania eukaryotic elongation Factor-1 beta protein is immunogenic and induces parasitological protection in mice against Leishmania infantum infection. Microbial Pathogenesis, 151, [104745]. (doi:10.1016/j.micpath.2021.104745).

Record type: Article

Abstract

Treatment for visceral leishmaniasis (VL) is hampered mainly by the toxicity and/or high cost of antileishmanial drugs. What is more, variability on sensitivity and/or specificity of diagnostic tests hinders effective disease management. In this context, prophylactic vaccination should be considered as a strategy to prevent disease. In the present study, immunogenicity of the Leishmania eukaryotic Elongation Factor-1 beta (EF1b) protein, classified as a Leishmania virulence factor, was evaluated in vitro and in vivo and tested, for the first time, as a vaccine candidate against Leishmania infantum infection. The antigen was administered as DNA vaccine or as recombinant protein (rEF1b) delivered in saponin. BALB/c mice immunization with a DNA plasmid and recombinant protein plus saponin induced development of specific Th1-type immunity, characterized by high levels of IFN-γ, IL-12, GM-CSF, both T cell subtypes and antileishmanial IgG2a isotype antibodies, before and after infection. This immunological response to the vaccines was corroborated further by parasitological analysis of the vaccinated and then challenged mice, which showed significant reductions in the parasite load in their liver, spleen, bone marrow and draining lymph nodes, when compared to the controls. Vaccination using rEF1b/saponin induced a more robust Th1 response and parasitological protection when compared to the DNA vaccine. Furthermore, in vitro analysis of lymphoproliferation, IFN-γ and IL-10 levels in human PBMC cultures showed as well development of a specific Th1-type response. In conclusion, data suggest that EF1b could be a promising vaccine candidate to protect against L. infantum infection.

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Accepted/In Press date: 15 January 2021
e-pub ahead of print date: 21 January 2021
Published date: February 2021
Additional Information: Funding Information: This work was supported by grant MR/R005850/1 from the Medical Research Council (VAccine deveLopment for complex Intracellular neglecteD pAThogEns - VALIDATE), UK, and grant APQ-408675/2018-7 from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) , Brazil. The authors also thank the Brazilian agencies Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) , CNPq and the Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) for the student scholarships. Funding Information: This work was supported by grant MR/R005850/1 from the Medical Research Council (VAccine deveLopment for complex Intracellular neglecteD pAThogEns - VALIDATE), UK, and grant APQ-408675/2018-7 from the Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq), Brazil. The authors also thank the Brazilian agencies Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES), CNPq and the Funda??o de Amparo ? Pesquisa do Estado de Minas Gerais (FAPEMIG) for the student scholarships. Publisher Copyright: © 2021 Elsevier Ltd
Keywords: DNA vaccine, Eukaryotic elongation Factor-1 beta, Leishmania infantum, Recombinant protein, Vaccine, Visceral leishmaniasis

Identifiers

Local EPrints ID: 447469
URI: http://eprints.soton.ac.uk/id/eprint/447469
ISSN: 0882-4010
PURE UUID: e02ad4d4-83c7-4918-95cd-38e2b807dfef
ORCID for Maria V Humbert: ORCID iD orcid.org/0000-0002-5728-6981

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Date deposited: 12 Mar 2021 17:30
Last modified: 17 Mar 2024 06:23

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Contributors

Author: Thais T.O. Santos
Author: Amanda Sanchez Machado
Author: Fernanda Fonseca Ramos
Author: Joao A Oliveira-da-Silva
Author: Daniela P Lage
Author: Grasiele S.V. Tavares
Author: Debora V.C. Mendoca
Author: Mariana S Cardoso
Author: Williane F Siqueira
Author: Vivian T Martins
Author: Fernanda Ludolf
Author: Thiago A.R. Reis
Author: Livia M. Carvalho
Author: Camila S. Freitas
Author: Raquel S Bandeira
Author: Alessandra M Silva
Author: Jamil S. Oliveira
Author: Ricardo L F Moreira
Author: Ricardo T Fujiwara
Author: Bruno M. Roatt
Author: Miguel A Chavez-Fumigalli
Author: Maria V Humbert ORCID iD
Author: Antonio L. Teixeira
Author: Eduardo Antonio Ferraz Coelho

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