Title

Biochemical characterization and vaccine potential of a heme-binding glutathione transferase from the adult hookworm Ancylostoma canium

Document Type

Journal Article

Publication Date

10-2005

Journal

Infection and Immunity

Volume

Volume 73, Issue 10

Inclusive Pages

6903-6911

Keywords

Ancylostoma--immunology; Ancylostomiasis--prevention & control; Carrier Proteins--immunology; Glutathione Transferase--immunology; Hemeproteins--immunology; Vaccines--genetics; Vaccines--immunology; Vaccines

Abstract

We report the cloning and expression of Ac-GST-1, a novel glutathione S-transferase from the adult hookworm Ancylostoma caninum, and its possible role in parasite blood feeding and as a vaccine target. The predicted Ac-GST-1 open reading frame contains 207 amino acids (mass, 24 kDa) and exhibited up to 65% amino acid identity with other nematode GSTs. mRNA encoding Ac-GST-1 was detected in adults, eggs, and larval stages, but the protein was detected only in adult hookworm somatic extracts and excretory/secretory products. Using antiserum to the recombinant protein, Ac-GST-1 was immunolocalized to the parasite hypodermis and muscle tissue and weakly to the intestine. Recombinant Ac-GST-1 was enzymatically active, as determined by conjugation of glutathione to a model substrate, and exhibited a novel high-affinity binding site for hematin. The possible role of Ac-GST-1 in parasite heme detoxification during hemoglobin digestion or heme uptake prompted interest in evaluating it as a potential vaccine antigen. Vaccination of dogs with Ac-GST-1 resulted in a 39.4% reduction in the mean worm burden and 32.3% reduction in egg counts compared to control dogs following larval challenge, although the reductions were not statistically significant. However, hamsters vaccinated with Ac-GST-1 exhibited statistically significant worm reduction (53.7%) following challenge with heterologous Necator americanus larvae. These studies suggest that Ac-GST-1 is a possible drug and vaccine target for hookworm infection.

Comments

This is a PubMed Central article. Click on link for full-text access.

Peer Reviewed

1

Open Access

1