title: Dissecting the Immune Response Elicited by WbALT-2, ALT MAP in Clinical Populations and Mouse Model: A Prophylactic Measure Against Lymphatic Filariasis.
abstract: BACKGROUND
  Abundant Larval Transcript (ALT) is one of the major groups of immune-dominant proteins produced by filarial worms during their larval stage. The major B-cell and T-cell epitopic domains of the ALT-2 antigen were mapped to develop a multiple antigenic peptide (MAP) prophylactic antigen against lymphatic filariasis.
  
  
  RESULTS
  ALT MAP was constructed by solid phase peptide synthesis. The reactivity of whole ALT protein and ALT MAP against clinical sera described a high reactivity of endemic normal sera against ALT MAP compared to WbALT-2 protein. The antibody isotype pattern revealed elevated levels of IgG1 and IgG2 against ALT MAP, followed by IgG3 and IgG4. In this study we also analyzed the immune response pattern elicited by ALT MAP, ALT in mice models, which revealed similar pattern of humoral response, while low T cell proliferation in ALT MAP groups. The low proliferation could be attributed to T/B epitope arrangement on the construct, MHC restriction, and incomplete signal delivery by T cell receptor.
  
  
  CONCLUSIONS
  The immunodominant epitopes in ALT MAP were found to play a crucial role in inducing high antigen specific proliferation. This revealed the significance of ALT MAP in stimulating innate immunity in offering protective immune response probably through the activation of complement cascade along with stimulation of cellular response. An improved understanding, including the construction of ALT MAP and parasite challenge study in jirds to determine the worm clearance would give a better insight in the characterization ALT MAP construct as a prophylactic vaccine candidate.
authors.affiliation: 1 Centre For Biotechnology, Anna University , Chennai, India .
authors.forename: Aparnaa
authors.initials: A
authors.lastname: Ramanathan
authors.affiliation: 1 Centre For Biotechnology, Anna University , Chennai, India .
authors.forename: Christiana
authors.initials: C
authors.lastname: Immanuel
authors.affiliation: 2 Department of Biochemistry, All India Institute of Medical Sciences , New Delhi, India.
authors.forename: Donthamsetty Nageswara
authors.initials: DN
authors.lastname: Rao
authors.affiliation: 1 Centre For Biotechnology, Anna University , Chennai, India .
authors.forename: Perumal
authors.initials: P
authors.lastname: Kaliraj
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology; D000947:Antigens, Helminth / Q000737:chemistry / Q000276:immunology*; D017178:Brugia malayi / Q000276:immunology*; D004195:Disease Models, Animal; D004605:Elephantiasis, Filarial / Q000276:immunology* / Q000469:parasitology* / Q000517:prevention & control; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000276:immunology; D007194:India; D007814:Larva; D051379:Mice; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D000939:Epitopes; D007074:Immunoglobulin G; D011994:Recombinant Proteins