Visceral leishmaniasis: An overview of vaccine adjuvants and their applications

Ratnapriya, Sneha; Keerti,; Sahasrabuddhe, Amogh A.; Dube, Anuradha

doi:10.1016/j.vaccine.2019.04.092

Cited by 39 publications

(16 citation statements)

References 144 publications

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“…First-generation vaccines used dead parasites administered with or without adjuvants, whereas second-generation vaccines used genetically-modified parasites or viruses expressing Leishmania genes encoding for recombinant proteins. Plasmid DNA-based vaccines that encode genes in eukaryotic expression vectors belong to a third generation 24 , 25 . However, none of these experimental vaccine candidates have satisfactorily progressed in human trials.…”

Section: Introductionmentioning

confidence: 99%

A candidate vaccine for human visceral leishmaniasis based on a specific T cell epitope-containing chimeric protein protects mice against Leishmania infantum infection

et al. 2020

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Leishmaniases are neglected diseases caused by infection with Leishmania parasites and there are currently no prophylactic vaccines. In this study, we designed in silico a synthetic recombinant vaccine against visceral leishmaniasis (VL) called ChimeraT, which contains specific T-cell epitopes from Leishmania Prohibitin, Eukaryotic Initiation Factor 5a and the hypothetical LiHyp1 and LiHyp2 proteins. Subcutaneous delivery of ChimeraT plus saponin stimulated a Th1 cell-mediated immune response and protected mice against L. infantum infection, significantly reducing the parasite load in distinct organs. ChimeraT/saponin vaccine stimulated significantly higher levels of IFN-γ, IL-12, and GM-CSF cytokines by both murine CD4 + and CD8 + T cells, with correspondingly low levels of IL-4 and IL-10. Induced antibodies were predominantly IgG2a isotype and homologous antigen-stimulated spleen cells produced significant nitrite as a proxy for nitric oxide. ChimeraT also induced lymphoproliferative responses in peripheral blood mononuclear cells from VL patients after treatment and healthy subjects, as well as higher IFN-γ and lower IL-10 secretion into cell supernatants. Thus, ChimeraT associated with a Th1 adjuvant could be considered as a potential vaccine candidate to protect against human disease.

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Section: Introductionmentioning

confidence: 99%

A candidate vaccine for human visceral leishmaniasis based on a specific T cell epitope-containing chimeric protein protects mice against Leishmania infantum infection

et al. 2020

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“…Finally, the thirdgeneration vaccines are composed of parasite antigens cloned in eukaryotic promoter vectors injected into the host muscle (3,4,80). Detailed reviews have previously summarized the vaccine antigens under research and those that were already tested in Phase II and Phase III trials (80)(81)(82), as well as the most suitable adjuvants (82). In this chapter, we will focus our review on the licensed vaccines against Leishmania.…”

Section: Vaccines Against Leishmaniasismentioning

confidence: 99%

“…Regarding the veterinary vaccines against ZVL, two preventive canine formulations have been registered in Brazil: Leishmune R in 2003 (80)(81)(82)(83)(84) and Leishtec R in 2008 (85). In Europe, where visceral leishmaniasis is also a canid zoonosis, two other vaccines were licensed: Canileish R in 2011 (86) and Letifend R (87) in 2016.…”

Section: Vaccines Against Leishmaniasismentioning

confidence: 99%

The Delay in the Licensing of Protozoal Vaccines: A Comparative History

Palatnik-de-Sousa

Nico

2020

Front. Immunol.

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“…Most protein-based vaccines fail to induce significant cellular responses without the use of adjuvants [ 31 ] and experimental VL vaccines are no exception [ 32 , 33 ]. Furthermore, adjuvants are necessary to increase the duration of protection and/or reduce the number of vaccine doses [ 34 ]. Previous studies have shown that saponins, which are glycosides capable of stimulating T-cells to produce Th1-type cytokines [ 35 ], have been successful as immuno-adjuvants with recombinant Leishmania proteins [ 36 , 37 , 38 , 39 , 40 , 41 ], chimeras [ 27 , 30 ], and synthetic peptides [ 42 , 43 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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Visceral leishmaniasis: An overview of vaccine adjuvants and their applications

Cited by 39 publications

References 144 publications

A candidate vaccine for human visceral leishmaniasis based on a specific T cell epitope-containing chimeric protein protects mice against Leishmania infantum infection

A candidate vaccine for human visceral leishmaniasis based on a specific T cell epitope-containing chimeric protein protects mice against Leishmania infantum infection

The Delay in the Licensing of Protozoal Vaccines: A Comparative History

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

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