Evaluation of immunomodulatory potential of recombinant histidyl-tRNA synthetase (rLdHisRS) protein of Leishmania donovani as a vaccine candidate against visceral leishmaniasis.

Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0370374 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-6254 (Electronic) Linking ISSN: 0001706X NLM ISO Abbreviation: Acta Trop Subsets: MEDLINE

Publication: Amsterdam : Elsevier
Original Publication: Basel.

Leishmania donovani*/genetics ; Leishmaniasis, Visceral*/prevention & control ; Vaccines* ; Leishmaniasis Vaccines*; Animals ; Mice ; Histidine-tRNA Ligase ; Escherichia coli ; Th1 Cells ; Cytokines ; Interleukin-12 ; Recombinant Proteins/genetics ; Epitopes ; Mice, Inbred BALB C ; Protozoan Proteins/genetics ; Antigens, Protozoan/genetics

Visceral leishmaniasis is neglected tropical protozoan disease caused by Leishmania donovani and are associated with high fatality rate in developing countries since prophylactic vaccines are not available. In the present study, we evaluated the immunomodulatory potential of L. donovani histidyl-tRNA synthetase (LdHisRS) and predicted the epitopes using immunoinformatic tools. Histidyl-tRNA synthetase (HisRS) is a class IIa aminoacyl t-RNA synthetase enzyme (aaRS) required for histidine incorporation into proteins during protein synthesis. The recombinant LdHisRS protein (rLdHisRS) was expressed in E coli BL-21cells, and its immunomodulatory role was assessed in J774A.1 murine macrophage and in BALB/c mice, respectively. LdHisRS specifically stimulated and triggered enhance cell proliferation, nitric oxide release and IFN-γ (70%; P < 0.001), and IL-12 (55.37%; P < 0.05) cytokine release in vitro, whereas BALB/c mice immunized with rLdHisRS show higher NO release (80.95%; P<0.001), higher levels of Th1 cytokines IFN-γ (14%; P < 0.05), TNF-α (34.93%; P < 0.001), and IL-12 (28.49%; P < 0.001) and robust IgG (p<0.001) and IgG2a (p<0.001) production. We also identified 20 Helper T-lymphocytes (HTLs), 30 cytotoxic T lymphocytes (CTLs), and 18 B-cell epitopes from HisRS protein of L. donovani. All these epitopes can be further used to make a multiepitope vaccine against L. donovani.
Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest.
(Copyright © 2023 Elsevier B.V. All rights reserved.)

Keywords: Cytokine release; Histidyl-tRNA synthetase; Immunomodulatory; L. donovani; Th1 response

EC 6.1.1.21 (Histidine-tRNA Ligase)
0 (Cytokines)
187348-17-0 (Interleukin-12)
0 (Vaccines)
0 (Recombinant Proteins)
0 (Epitopes)
0 (Leishmaniasis Vaccines)
0 (Protozoan Proteins)
0 (Antigens, Protozoan)

Date Created: 20230306 Date Completed: 20230404 Latest Revision: 20230404

20231215

10.1016/j.actatropica.2023.106867

36878386