title: Immunogenicity and immune modulatory effects of in silico predicted L. donovani candidate peptide vaccines.
abstract: Visceral leishmaniasis (VL) is a serious parasitic disease for which control measures are limited and drug resistance is increasing. First and second generation vaccine candidates have not been successful. The goal of the present study was to select possibly immunogenic L. donovani donovani GP63 peptides using immunoinformatics tools and to test their immunogenicity in vitro. The amino acid sequence of L. donovani donovani GP63 [GenBank accession: ACT31401] was screened using the EpiMatrix algorithm for putative T cell epitopes that would bind to the most common HLA class II alleles (DRB1*1101 and DRB1*0804) among at-risk populations. Four T cell epitopes were selected from nine potential candidates. Stimulation of whole blood from healthy volunteers using the peptides separately produced mean IFN-γ and IL-4 levels that were not significantly different from negative controls, while the pooled peptides produced a moderate IFN-γ increase in some volunteers. However, mean IL-10 levels were significantly reduced for all individuals compared with controls. The immunogenicity of these epitopes may be harnessed most effectively in a vaccine delivered in combination with immune-modulating adjuvants.
authors.affiliation: Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
authors.forename: Mona E E
authors.initials: ME
authors.lastname: Elfaki
authors.forename: Eltahir A G
authors.initials: EA
authors.lastname: Khalil
authors.forename: Anne S
authors.initials: AS
authors.lastname: De Groot
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Musa
authors.forename: Andres
authors.initials: A
authors.lastname: Gutierrez
authors.forename: Brima M
authors.initials: BM
authors.lastname: Younis
authors.forename: Kawthar A M
authors.initials: KA
authors.lastname: Salih
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: El-Hassan
mesh_terms: D000328:Adult; D019295:Computational Biology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007893:Leishmania donovani / Q000235:genetics / Q000276:immunology*; D054332:Leishmaniasis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D018984:Epitopes, T-Lymphocyte; D054332:Leishmaniasis Vaccines; D022223:Vaccines, Subunit; D016753:Interleukin-10; D007371:Interferon-gamma; D008666:Metalloendopeptidases; C055146:glycoprotein gp63, Leishmania