Vaccination with recombinant aspartic hemoglobinase reduces parasite load and blood loss after hookworm infection in dogs

• Published in: PLoS medicine Vol. 2; no. 10; p. e295
• Main Authors: Loukas, Alex, Bethony, Jeffrey M, Mendez, Susana, Fujiwara, Ricardo T, Goud, Gaddam Narsa, Ranjit, Najju, Zhan, Bin, Jones, Karen, Bottazzi, Maria Elena, Hotez, Peter J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.10.2005; Public Library of Science (PLoS)
• Subjects: Allergy/Immunology; Amino Acid Sequence; Ancylostoma - pathogenicity; Anemia; Anemia - etiology; Anemia - prevention & control; Animals; Antibodies; Antibody Formation; Antigens; Aspartic Acid Endopeptidases - pharmacology; Aspartic Acid Endopeptidases - therapeutic use; Developing countries; Dogs; Enzymes; Glycerol; Hemoglobin; Hemorrhage - etiology; Hemorrhage - prevention & control; Hookworm Infections - drug therapy; Hookworm Infections - pathology; Hookworm Infections - veterinary; Immunization; Immunoglobulin G - analysis; Immunology and allergy; Infections; Infectious Diseases; LDCs; Male; Microbiology; Molecular Sequence Data; Nematodes; Parasites; Parasitology; Recombinant Proteins; Vaccination - veterinary; Vaccines; United States > US; Amino Acid Sequence; Anemia; Immunoglobulin G; Vaccination; Ancylostoma; Molecular Sequence Data; Male; Recombinant Proteins; Hemorrhage; Animals; Aspartic Acid Endopeptidases; Dogs; Antibody Formation; Hookworm Infections
• ISSN: 1549-1676; 1549-1277; 1549-1676
• DOI: 10.1371/journal.pmed.0020295

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. 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. 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.