Comparative evaluation of meglumine antimoniate encapsulated in a mixture of conventional and PEGylated liposomes and immunotherapy using an anti-canine IL-10 receptor-blocking monoclonal antibody on canine visceral leishmaniasis

Mol Immunol. 2022 Jan:141:70-78. doi: 10.1016/j.molimm.2021.11.011. Epub 2021 Nov 20.

Abstract

This study compared the therapeutic potential of the chemotherapy using meglumine antimoniate encapsulated in a mixture of conventional and PEGylated liposomes (Nano Sbv) and immunotherapy with anti-canine IL-10 receptor-blocking monoclonal antibody (Anti IL-10R) on canine visceral leishmaniasis (CVL). Twenty mongrel dogs naturally infected by L. infantum, displaying clinical signs of visceral leishmaniasis were randomly divided in two groups. In the first one, nine dogs received six intravenous doses of a mixture of conventional and PEGylated liposomes containing meglumine antimoniate at 6.5 mg Sb/kg/dose. In the second one, eleven dogs received two intramuscular doses of 4 mg of anti-canine IL-10 receptor-blocking monoclonal antibody. The animals were evaluated before (T0) and 30, 90, and 180 days after treatments. Our major results demonstrated that both treatments were able to maintain hematological and biochemical parameters, increase circulating T lymphocytes subpopulations, increase the IFN-γ producing T-CD4 lymphocytes, restore the lymphoproliferative capacity and improve the clinical status. However, although these improvements were observed in the initial post-treatment times, they did not maintain until the end of the experimental follow-up. We believe that the use of booster doses or the association of chemotherapy and immunotherapy (immunochemotherapy) is promising to improve the effectiveness of treating CVL for improving the clinical signs and possibly reducing the parasite burden in dogs infected with Leishmania infantum.

Keywords: Anti-canine IL-10 receptor-blocking monoclonal antibody; Canine visceral leishmaniasis; Chemotherapy; Immunotherapy; Leishamania infantum; Liposomal meglumine antimoniate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allopurinol / pharmacology
  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / metabolism
  • Dog Diseases / drug therapy*
  • Dog Diseases / metabolism
  • Dogs
  • Immunologic Factors / metabolism
  • Immunotherapy / methods
  • Leishmania infantum / drug effects
  • Leishmaniasis, Visceral / drug therapy*
  • Leishmaniasis, Visceral / metabolism
  • Liposomes / chemistry*
  • Meglumine Antimoniate / pharmacology*
  • Organometallic Compounds / pharmacology
  • Polyethylene Glycols / chemistry*
  • Receptors, Interleukin-10 / antagonists & inhibitors*

Substances

  • Antibodies, Monoclonal
  • Immunologic Factors
  • Liposomes
  • Organometallic Compounds
  • Receptors, Interleukin-10
  • Polyethylene Glycols
  • Allopurinol
  • Meglumine Antimoniate