Surrogate markers of immunity to Leishmania major in leishmanin skin test negative individuals from an endemic area re-visited

Susanne Nylén, Ali Khamesipour, Akram Mohammadi, Reza Jafari-Shakib, Liv Eidsmo, Sassan Noazin, Farrokh Modabber, Hannah Akuffo

Research output: Contribution to journalArticlepeer-review

Abstract

Background: In the screening of vaccine candidates it is important to select candidates that evoke immune responses associated with protection. Valid surrogate markers against human leishmaniasis are still lacking. Methods: A controlled injection of live Leishmania known as leishmanization, (LZ), was used to evaluate vaccine (alum-precipitated autoclaved Leishmania major with BCG) efficacy and more accurately define surrogate markers of immunity to leishmaniasis in humans. Cellular immune responses to this artificial infection were monitored in the volunteers prior to and 9 months post infection. Comparisons were made between those who developed a lesion after infection and those who did not. Results: In the volunteers monitored there was no significant difference in LST, IFNγ production, or source of IFNγ between those who developed a lesion and those who did not after LZ, with the exception that ulcer development was associated with an enhanced number of IFNγ secreting CD4+ CD45RA- (memory) T cells. Discussion: Ulcer development following LZ was lower than anticipated by a pilot study (47% versus 78%) using the same stabilate several years earlier. While this may be an effect of low viability/virulence of the LZ inocula, alternative explanations are also possible. The IFNγ responses in the study subjects were significantly lower compared to volunteers with previous history of cutaneous leishmaniasis. The findings raise the possibility that the selection of LST-negative volunteers in an endemic area may bias the study towards potentially non/low L. major-reactive volunteers.

Original languageEnglish (US)
Pages (from-to)6944-6954
Number of pages11
JournalVaccine
Volume24
Issue number47-48
DOIs
StatePublished - Nov 17 2006
Externally publishedYes

Keywords

  • IFNγ
  • LST
  • LZ
  • Leishmania
  • T cell
  • vaccine

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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