TY - JOUR
T1 - Biochemical characterization and vaccine potential of a heme-binding glutathione transferase from the adult hookworm Ancylostoma caninum
AU - Zhan, Bin
AU - Liu, Sen
AU - Perally, Samirah
AU - Xue, Jian
AU - Fujiwara, Ricardo
AU - Brophy, Peter Michael
AU - Xiao, Shuhua
AU - Liu, Yueyuan
AU - Feng, Jianjun
AU - Williamson, Angela
AU - Wang, Yan
AU - Bueno, Lilian L.
AU - Mendez, Susana
AU - Goud, Gaddam
AU - Bethony, Jeffrey M.
AU - Hawdon, John M.
AU - Loukas, Alex
AU - Jones, Karen
AU - Hotez, Peter J.
N1 - Zhan, B., Liu, S., Perally, S., Xue, J., Fujiwara, R., Brophy, P., Xiao, S. H., Liu, Y. Y., Feng, J. J., Williamson, A., Wang, Y., Bueno, L. L., Mendez, S., Goud, G., Bethony, J. M., Hawdon, J. M., Loukas, A., Jones, K., Hotez, P. J. (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.
Sponsorship: Human Hookworm Vaccine Initiative of the Sabin Vaccine Institute / Bill and Melinda Gates Foundation. / BBSRC
PY - 2005/10
Y1 - 2005/10
N2 - 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.
AB - 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.
U2 - 10.1128/IAI.73.10.6903-6911.2005
DO - 10.1128/IAI.73.10.6903-6911.2005
M3 - Article
C2 - 16177370
SN - 0019-9567
VL - 73
SP - 6903
EP - 6911
JO - Infection and Immunity
JF - Infection and Immunity
IS - 10
ER -