title: Bacterial lipid modification enhances immunoprophylaxis of filarial abundant larval transcript-2 protein in Mastomys model.
abstract: As in many other parasitic diseases, efficacious vaccine for lymphatic filariasis has been elusive for want of new approaches leaving billions of people either debilitated or at risk. With multiple B- and T-cell epitopes, the abundant larval transcript-2 (ALT-2) of the filarial worm, Brugia malayi, has been shown to be a promising immunoprophylactic target. To enhance its efficacy, it was lipid modified using our recently developed protein engineering tool, which then offered 30% more immunoprotection (49 vs. 79%) in Mastomys coucha model. Sustained high levels of IFN-γ (about 100 times) and high antibody titres (10-fold) elicited by lipid-modified ALT-2, as compared to the native form, indicated the maintenance of Th1/Th2 balance that is impaired in filariasis. Thus, this study provides the basis for developing efficacious vaccines for filariasis and other parasitic diseases by exploiting bacterial lipid modification.
authors.affiliation: Centre for Biotechnology, Anna University, Chennai, Tamilnadu, India.
authors.forename: S
authors.initials: S
authors.lastname: Sharmila
authors.forename: I
authors.initials: I
authors.lastname: Christiana
authors.forename: P
authors.initials: P
authors.lastname: Kiran
authors.forename: M V R
authors.initials: MV
authors.lastname: Reddy
authors.forename: K
authors.initials: K
authors.lastname: Sankaran
authors.forename: P
authors.initials: P
authors.lastname: Kaliraj
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood / Q000276:immunology; D000947:Antigens, Helminth / Q000276:immunology*; D017178:Brugia malayi / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004605:Elephantiasis, Filarial / Q000276:immunology / Q000517:prevention & control*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D004926:Escherichia coli / Q000235:genetics; D005989:Glycerides / Q000276:immunology; D006801:Humans; D007114:Immunization; D007814:Larva / Q000276:immunology; D008055:Lipids / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051189:Murinae; D015202:Protein Engineering; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014612:Vaccines / Q000276:immunology
chemical_list: D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D005989:Glycerides; D008055:Lipids; D011994:Recombinant Proteins; D014612:Vaccines; C114956:2-palmitoylglycerol
keywords: Brugia malayi; Mastomys; abundant larval transcript; bacterial lipid modification; immunoprophylaxis; lymphatic filariasis