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

Authors

Bin Zhan, George Washington UniversityFollow
Sen Liu
Samirah Perally
Jian XueFollow
Ricardo T. Fujiwara, George Washington University
Peter Brophy
Shuhua Xiao
Yueyuan Liu
Jianjun Feng
Angela Williamson
Yan Wang
Lilian L. Bueno
Susana Mendez, George Washington University
Gaddam Narsa Goud, George Washington University
Jeffrey M. Bethony, George Washington UniversityFollow
John Hawdon, George Washington UniversityFollow
Alex Loukas, James Cook University, Cairns, AustraliaFollow
Karen C. Jones, George Washington UniversityFollow
Peter J. Hotez, George Washington University

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

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APA Citation

Zhan, B., Liu, S., Perally, S., Xue, J., Fujiwara, R. et al. (2005). Biochemical characterization and vaccine potential of a heme-binding glutathione transferase from the adult hookworm Ancylostoma caninum. Infection and Immunity, 73(10), 6903-6911.

Peer Reviewed

1

Open Access

1