Vaccination with recombinant aspartic hemoglobinase reduces parasite load and blood loss after hookworm infection in dogs.
BACKGROUND
Hookworms infect 730 million people in developing countries where they are a leading cause of intestinal blood loss and iron-deficiency anemia. At the site of attachment to the host, adult hookworms ingest blood and lyse the erythrocytes to release hemoglobin. The parasites subsequently digest hemoglobin in their intestines using a cascade of proteolysis that begins with the Ancylostoma caninum aspartic protease 1, APR-1.


RESULTS
We show that vaccination of dogs with recombinant Ac-APR-1 induced antibody and cellular responses and resulted in significantly reduced hookworm burdens (p = 0.056) and fecal egg counts (p = 0.018) in vaccinated dogs compared to control dogs after challenge with infective larvae of A. caninum. Most importantly, vaccinated dogs were protected against blood loss (p = 0.049) and most did not develop anemia, the major pathologic sequela of hookworm disease. IgG from vaccinated animals decreased the catalytic activity of the recombinant enzyme in vitro and the antibody bound in situ to the intestines of worms recovered from vaccinated dogs, implying that the vaccine interferes with the parasite's ability to digest blood.


CONCLUSIONS
To the best of our knowledge, this is the first report of a recombinant vaccine from a hematophagous parasite that significantly reduces both parasite load and blood loss, and it supports the development of APR-1 as a human hookworm vaccine.
Loukas
Alex
A
Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research, Brisbane, Queensland, Australia. alex.loukas@qimr.edu.au
Bethony
Jeffrey M
JM
Mendez
Susana
S
Fujiwara
Ricardo T
RT
Goud
Gaddam Narsa
GN
Ranjit
Najju
N
Zhan
Bin
B
Jones
Karen
K
Bottazzi
Maria Elena
ME
Hotez
Peter J
PJ
D000595:Amino Acid Sequence; D000722:Ancylostoma / Q000472:pathogenicity; D000740:Anemia / Q000209:etiology / Q000517:prevention & control; D000818:Animals; D000917:Antibody Formation; D016282:Aspartic Acid Endopeptidases / Q000494:pharmacology* / Q000627:therapeutic use*; D004285:Dogs; D006470:Hemorrhage / Q000209:etiology / Q000517:prevention & control; D006725:Hookworm Infections / Q000188:drug therapy* / Q000473:pathology / Q000662:veterinary*; D007074:Immunoglobulin G / Q000032:analysis; D008297:Male; D008969:Molecular Sequence Data; D011994:Recombinant Proteins; D014611:Vaccination / Q000662:veterinary*
D007074:Immunoglobulin G; D011994:Recombinant Proteins; D016282:Aspartic Acid Endopeptidases; C089643:plasmepsin