Surrogate markers of immunity to Leishmania major in leishmanin skin test negative individuals from an endemic area re-visited.
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.
Nylén
Susanne
S
Microbiology and Tumor biology Center (MTC), Karolinska Institutet, Stockholm, Sweden.
Khamesipour
Ali
A
Mohammadi
Akram
A
Jafari-Shakib
Reza
R
Eidsmo
Liv
L
Noazin
Sassan
S
Modabber
Farrokh
F
Akuffo
Hannah
H
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
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000953:Antigens, Protozoan; D015415:Biomarkers; D016207:Cytokines; C041524:aluminum sulfate; D007371:Interferon-gamma