title: Surrogate markers of immunity to Leishmania major in leishmanin skin test negative individuals from an endemic area re-visited.
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, IFNgamma production, or source of IFNgamma 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 IFNgamma secreting CD4(+) CD45RA(-) (memory) T cells.
  
  
  CONCLUSIONS
  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 IFNgamma 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.
authors.affiliation: Microbiology and Tumor biology Center (MTC), Karolinska Institutet, Stockholm, Sweden.
authors.forename: Susanne
authors.initials: S
authors.lastname: Nylén
authors.forename: Ali
authors.initials: A
authors.lastname: Khamesipour
authors.forename: Akram
authors.initials: A
authors.lastname: Mohammadi
authors.forename: Reza
authors.initials: R
authors.lastname: Jafari-Shakib
authors.forename: Liv
authors.initials: L
authors.lastname: Eidsmo
authors.forename: Sassan
authors.initials: S
authors.lastname: Noazin
authors.forename: Farrokh
authors.initials: F
authors.lastname: Modabber
authors.forename: Hannah
authors.initials: H
authors.lastname: Akuffo
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000534:Alum Compounds; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D016207:Cytokines / Q000096:biosynthesis; D004311:Double-Blind Method; D019353:Endemic Diseases; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D008297:Male; D009163:Mycobacterium bovis / Q000276:immunology; D010641:Phenotype; D012882:Skin Tests
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000953:Antigens, Protozoan; D015415:Biomarkers; D016207:Cytokines; C041524:aluminum sulfate; D007371:Interferon-gamma