Evolution of antigen-specific immune responses in cutaneous leishmaniasis patients

Parasite Immunol. 2021 Apr;43(4):e12814. doi: 10.1111/pim.12814. Epub 2021 Feb 15.

Abstract

Aims: Despite immunization appearing to be the most appropriate strategy for long-term control of the vector-borne leishmaniases, no sustainable vaccine is currently available against any form of leishmaniasis. We therefore evaluated, in the context of vaccine antigen candidates, antigen-specific immune response at various stages of cutaneous leishmaniasis (CL).

Methods and results: Peripheral blood mononuclear cells (PBMC) isolated from healthy volunteers and CL patients (caused by either Leishmania major or L tropica) were incubated with crude Leishmania proteins (soluble Leishmania antigen; SLA), single recombinant proteins (TSA, LeIF, LmSTI1) or chimeric fusion proteins (LEISH-F2 and LEISH-F3). The concentrations of immune modulatory cytokines were then determined. While we did not detect appreciable antigen-specific IL-5 secretion, SLA induced secretion of interleukin (IL)-10 in cultures from early active lesion CL patients and even from healthy individuals. Conversely, interferon (IFN)-γ responses to SLA and recombinant proteins followed a similar pattern, developing only in the late active CL lesion phase. Once established, antigen-specific IFN-γ responses persisted in cured CL patients.

Conclusion: Together, our results provide further insight into the development of immune responses during CL and further validate the selection of LEISH-F2 and LEISH-F3 as vaccine antigen candidates.

Keywords: cutaneous leishmaniasis; proinflammatory cytokines; protein; vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Protozoan / immunology*
  • Cytokines / immunology
  • Humans
  • Interferon-gamma
  • Leishmaniasis, Cutaneous / immunology*
  • Leishmaniasis, Cutaneous / prevention & control*
  • Leukocytes, Mononuclear*
  • Protozoan Proteins / immunology*

Substances

  • Antigens, Protozoan
  • Cytokines
  • Protozoan Proteins
  • Interferon-gamma