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Validating Immunomodulatory Responses of r- Ld ODC Protein and Its Derived HLA-DRB1 Restricted Epitopes against Visceral Leishmaniasis in BALB/c Mice.

Rajkishor PandeyRohit Kumar GautamSimran SharmaMebrahtu G TedlaVijay MahanteshManas Ranjan DikhitAkhilesh KumarKrishna PandeySanjiva Bimal
Published in: Pathogens (Basel, Switzerland) (2022)
Vaccination is considered the most appropriate way to control visceral leishmaniasis (VL). With this background, the r- Ld ODC protein as well as its derived HLA-DRB1-restricted synthetic peptides (P1: RLMPSAHAI, P2: LLDQYQIHL, P3: GLYHSFNCI, P4: AVLEVLSAL, and P5: RLPASPAAL) were validated in BALB/c mice against visceral leishmaniasis. The study was initiated by immunization of the r- Ld ODC protein as well as its derived peptides cocktail with adjuvants (r-CD2 and MPL-A) in different mice groups, separately. Splenocytes isolated from the challenged and differentially immunized mice group exhibited significantly higher IFN-γ secretion, which was evidenced by the increase in the expression profile of intracellular CD4+IFN-γ T cells. However, the IL-10 secretion did not show a significant increase against the protein and peptide cocktail. Subsequently, the study confirmed the ability of peptides as immunoprophylactic agents, as the IE-I/AD-I molecule overexpressed on monocytes and macrophages of the challenged mice group. The parasitic load in macrophages of the protein and peptides cocktail immunized mice groups, and T cell proliferation rate, further established immunoprophylactic efficacy of the r- Ld ODC protein and peptide cocktail. This study suggests that the r- Ld ODC protein, as well as its derived HLA-DRB1-restricted synthetic peptides, have immunoprophylactic potential and can activate other immune cells' functions towards protection against visceral leishmaniasis. However, a detailed study in a humanized mice model can explore its potential as a vaccine candidate.
Keyphrases
  • amino acid
  • high fat diet induced
  • protein protein
  • cell proliferation
  • immune response
  • dendritic cells
  • type diabetes
  • metabolic syndrome
  • adipose tissue
  • small molecule
  • risk assessment
  • climate change