Evaluation of ex vivo human immune response against candidate antigens for a visceral leishmaniasis vaccine

Am J Trop Med Hyg. 2010 May;82(5):808-13. doi: 10.4269/ajtmh.2010.09-0341.

Abstract

People cured from visceral leishmaniasis (VL) develop protection mediated by Th1-type cellular responses against new infections. We evaluated cytokine responses against 6 defined candidate vaccine antigens in 15 cured VL subjects and 5 healthy endemic controls with no evidence of previous exposure to Leishmania parasites. Of the 6 cytokines examined, only interferon-gamma (IFN-gamma) differentiated cured VL patients from non-exposed individuals, with cured patients mounting a significantly higher IFN-gamma response to a crude parasite antigen preparation. Among candidate vaccine antigens tested, the largest number of cured subjects recognized cysteine proteinase B, leading to heightened IFN-gamma responses, followed by sterol 24-c-methyltransferase. These two antigens were the most immunogenic and protective antigens in a murine VL model, indicating a relationship between T cell recall responses of humans cured from VL and protective efficacy in an experimental model. Further studies may help prioritize antigens for clinical development of a subunit vaccine against VL.

Publication types

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

MeSH terms

  • Adult
  • Animals
  • Antigens, Protozoan / immunology*
  • Biological Assay
  • Cytokines / biosynthesis
  • Cytokines / blood
  • Drug Evaluation, Preclinical
  • Female
  • Humans
  • Interferon-gamma / biosynthesis
  • Leishmania / immunology
  • Leishmaniasis, Visceral / prevention & control*
  • Lymphocyte Activation / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Protozoan Vaccines / immunology*
  • Spleen / cytology

Substances

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