title: Recombinant trehalose-6-phosphate phosphatase of Brugia malayi cross-reacts with human Wuchereria bancrofti immune sera and engenders a robust protective outcome in mice.
abstract: Trehalose-6-phosphate phosphatase of Brugia malayi (Bm-TPP) represents an attractive vaccine candidate because it is present in all the major life stages of parasite, but is absent in mammals. We have previously cloned, purified and biochemically characterized Bm-TPP. In the present study, we investigated the cross-reactivity of recombinant Bm-TPP (r-Bm-TPP) with the sera of human bancroftian patients belonging to different disease categories. In silico study using bioinformatics tool demonstrated that Bm-TPP is highly immunogenic in nature. BALB/c mice administered with r-Bm-TPP alone or in combination with Freund's complete adjuvant (FCA) generated a strong IgG response. Further investigations on the antibody isotypes showed generation of a mixed T helper cell response which was marginally biased towards Th1 phenotype. r-Bm-TPP with or without adjuvant lead to significantly increased accumulation of CD4+ and CD8+ T cells in the spleen of infected mice and increased the activation of peritoneal macrophages. Additionally, r-Bm-TPP enhanced the production of both proinflammatory (IL-2, IFN-γ) and anti-inflammatory (IL-4, IL-10) cytokines and mice immunized with r-Bm-TPP alone or in combination with FCA showed 54.5% and 67% protection respectively against B. malayi infective larvae challenge. Taken together, our findings suggest that Bm-TPP is protective in nature and might be a potential candidate for development of vaccine against lymphatic filarial infections.
authors.affiliation: Division of Parasitology, Central Drug Research Institute, A unit of Council of Scientific and Industrial Research, Lucknow-226001, UP, India.
authors.forename: Susheela
authors.initials: S
authors.lastname: Kushwaha
authors.forename: Prashant Kumar
authors.initials: PK
authors.lastname: Singh
authors.forename: Jyoti
authors.initials: J
authors.lastname: Gupta
authors.forename: Vishal Kumar
authors.initials: VK
authors.lastname: Soni
authors.forename: Shailja
authors.initials: S
authors.lastname: Misra-Bhattacharya
mesh_terms: D000595:Amino Acid Sequence; D000704:Analysis of Variance; D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D017178:Brugia malayi / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D019295:Computational Biology; D003198:Computer Simulation; D003429:Cross Reactions; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004605:Elephantiasis, Filarial / Q000276:immunology; D015801:Helminth Proteins / Q000276:immunology* / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology / Q000378:metabolism; D008264:Macrophages; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010744:Phosphoric Monoester Hydrolases / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D014614:Vaccines, Synthetic / Q000276:immunology; D014958:Wuchereria bancrofti / Q000235:genetics / Q000276:immunology*
chemical_list: D000909:Antibodies, Helminth; D016207:Cytokines; D015801:Helminth Proteins; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; C023178:trehalose-phosphatase; D010744:Phosphoric Monoester Hydrolases