title: Effect of vaccination with a recombinant fusion protein encoding an astacinlike metalloprotease (MTP-1) secreted by host-stimulated Ancylostoma caninum third-stage infective larvae.
abstract: Laboratory dogs were vaccinated intramuscularly with a recombinant fusion protein (expressed and isolated from Escherichia coli) formulated with the Glaxo SmithKline Adjuvant System 02 (AS02). The fusion protein encoded Ac-MTP-1, a developmentally regulated astacinlike metalloprotease secreted by host-stimulated Ancylostoma caninum third-stage larvae (L3). Control dogs were injected intramuscularly with an equivalent amount of AS02 adjuvant alone. The vaccinated and control dogs were then challenged by s.c. injection of 500 L3 of the canine hookworm A. caninum. The vaccinated dogs developed prechallenge immunoglobulin G2 (IgG2) antibody responses specific to anti-Ac-MTP-1-fusion protein with titers ranging between 1:40,000 and 1:364,000, whereas they developed antigen-specific immunoglobulin E antibody responses with titers ranging between 1:500 and 1:1,500. By immunoblotting, canine sera obtained from the vaccinated dogs recognized a protein of the estimated apparent molecular weight of Ac-MTP-1 in activated L3 secretory products. Spearman rank order correlations between the canine intestinal adult hookworm burden and quantitative egg counts at necropsy and anti-Ac-MTP-1 IgG2 antibody titers revealed a statistically significant inverse association (r = -0.89; P = 0.04), suggesting that this molecule offers promise as a recombinant vaccine.
authors.affiliation: Department of Microbiology and Tropical Medicine and Sabin Vaccine Institute, The George Washington University Medical Center, 2300 Eye Street NW, Washington, DC 20037, USA. mtmpjh@gwumc.edu
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Hotez
authors.forename: James
authors.initials: J
authors.lastname: Ashcom
authors.forename: Bin
authors.initials: B
authors.lastname: Zhan
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Bethony
authors.forename: Alex
authors.initials: A
authors.lastname: Loukas
authors.forename: John
authors.initials: J
authors.lastname: Hawdon
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Qun
authors.initials: Q
authors.lastname: Jin
authors.forename: Karen C
authors.initials: KC
authors.lastname: Jones
authors.forename: Azra
authors.initials: A
authors.lastname: Dobardzic
authors.forename: Reshad
authors.initials: R
authors.lastname: Dobardzic
authors.forename: Janelle
authors.initials: J
authors.lastname: Bolden
authors.forename: Idong
authors.initials: I
authors.lastname: Essiet
authors.forename: Walter
authors.initials: W
authors.lastname: Brandt
authors.forename: Philip K
authors.initials: PK
authors.lastname: Russell
authors.forename: Bernard C
authors.initials: BC
authors.lastname: Zook
authors.forename: Brian
authors.initials: B
authors.lastname: Howard
authors.forename: Marco
authors.initials: M
authors.lastname: Chacon
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000722:Ancylostoma / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D000724:Ancylostomiasis / Q000517:prevention & control*; D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis; D004285:Dogs; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007273:Injections, Intramuscular; D007422:Intestines / Q000469:parasitology; D007814:Larva / Q000201:enzymology; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000909:Antibodies, Helminth; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D007073:Immunoglobulin E; C456261:MTP-1 protein, Ancylostoma caninum; D008666:Metalloendopeptidases