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Liposomal Formulation of ChimeraT, a Multiple T-Cell Epitope-Containing Recombinant Protein, Is a Candidate Vaccine for Human Visceral Leishmaniasis

1
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 30130-100, Brazil
2
Laboratório de Imunopatologia, Núcleo de Pesquisas em Ciências Biológicas/NUPEB, Departamento de Ciências Biológicas, Insituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais 35400-000, Brazil
3
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil
4
Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, Santa Catarina 88806-000, Brazil
5
Neisseria Research Group, Molecular Microbiology, School of Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton SO16 6YD, UK
*
Author to whom correspondence should be addressed.
Senior co-authors.
Vaccines 2020, 8(2), 289; https://doi.org/10.3390/vaccines8020289
Received: 7 May 2020 / Revised: 1 June 2020 / Accepted: 6 June 2020 / Published: 9 June 2020
Background: Leishmaniases are neglected diseases caused by infection with Leishmania parasites and there are no human vaccines in use routinely. The purpose of this study was to examine the immunogenicity of ChimeraT, a novel synthetic recombinant vaccine against visceral leishmaniasis (VL), incorporated into a human-compatible liposome formulation. Methods: BALB/c mice were immunized subcutaneously with ChimeraT/liposome vaccine, ChimeraT/saponin adjuvant, or ChimeraT/saline and immune responses examined in vitro and in vivo. Results: Immunization with the ChimeraT/liposome formulation induced a polarized Th1-type response and significant protection against L. infantum infection. ChimeraT/liposome vaccine stimulated significantly high levels of interferon (IFN)-γ, interleukin (IL)-12, and granulocyte macrophage-colony stimulating factor (GM-CSF) cytokines by both CD4 and CD8 T-cells, with correspondingly lower levels of IL-4 and IL-10 cytokines. Induced antibodies were predominantly IgG2a isotype, and homologous antigen-stimulated spleen cells produced significant nitrite as a proxy for nitric oxide (NO). Furthermore, we examined a small number of treated VL patients and found higher levels of circulating anti-ChimeraT protein IgG2 antibodies, compared to IgG1 levels. Conclusions: Overall, the liposomal formulation of ChimeraT induced a protective Th1-type immune response and thus could be considered in future studies as a vaccine candidate against human VL. View Full-Text
Keywords: ChimeraT; visceral leishmaniasis; vaccine; liposome; saponin; Th1-type immunity ChimeraT; visceral leishmaniasis; vaccine; liposome; saponin; Th1-type immunity
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Lage, D.P.; Ribeiro, P.A.; Dias, D.S.; Mendonça, D.V.; Ramos, F.F.; Carvalho, L.M.; Steiner, B.T.; Tavares, G.S.; Martins, V.T.; Machado, A.S.; Oliveira-da-Silva, J.A.; Santos, T.T.; Freitas, C.S.; Oliveira, J.S.; Roatt, B.M.; Machado-de-Ávila, R.A.; Humbert, M.V.; Christodoulides, M.; Coelho, E.A. Liposomal Formulation of ChimeraT, a Multiple T-Cell Epitope-Containing Recombinant Protein, Is a Candidate Vaccine for Human Visceral Leishmaniasis. Vaccines 2020, 8, 289.

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