Effect of vaccination with a recombinant fusion protein encoding an astacinlike metalloprotease (MTP-1) secreted by host-stimulated Ancylostoma caninum third-stage infective larvae.
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.
Hotez
Peter J
PJ
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
Ashcom
James
J
Zhan
Bin
B
Bethony
Jeffrey
J
Loukas
Alex
A
Hawdon
John
J
Wang
Yang
Y
Jin
Qun
Q
Jones
Karen C
KC
Dobardzic
Azra
A
Dobardzic
Reshad
R
Bolden
Janelle
J
Essiet
Idong
I
Brandt
Walter
W
Russell
Philip K
PK
Zook
Bernard C
BC
Howard
Brian
B
Chacon
Marco
M
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
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