TY - JOUR
T1 - Molecular Cloning, Biochemical Characterization, and Partial Protective Immunity of the Heme-Binding Glutathione S-Transferases from the Human Hookworm Necator americanus
AU - Zhan, Bin
AU - Perally, Samirah
AU - Brophy, Peter M.
AU - Xue, Jian
AU - Goud, Gaddam
AU - Liu, Sen
AU - Deumic, Vehid
AU - de Oliveira, Luciana
AU - Bethony, Jeffrey
AU - Bottazzi, Maria Elena
AU - Jiang, Desheng
AU - Gillespie, Portia
AU - Xiao, Shu-hua
AU - Gupta, Richi
AU - Loukas, Alex
AU - Ranjit, Najju
AU - Lustigman, Sara
AU - Hotez, Peter
AU - Oksov, Yelena
N1 - Zhan, B., Perally, S., Brophy, P. M., Xue, J., Goud, G., Liu, S., Deumic, V., de Oliveira, L., Bethony, J., Bottazzi, M. E., Jiang, D., Gillespie, P., Xiao, S., Gupta, R., Loukas, A., Ranjit, N., Lustigman, S., Hotez, P. (2010). Molecular cloning, biochemical characterization, and partial protective immunity of the heme-binding glutathione transferases from the human hookworm Necator americanus. Infection and Immunity, 78 (4), 1552-1563.
IMPF: 04.09
PY - 2010/4
Y1 - 2010/4
N2 - Hookworm glutathione S-transferases (GSTs) are critical for parasite blood feeding and survival and represent potential targets for vaccination. Three cDNAs, each encoding a full-length GST protein from the human hookworm Necator americanus (and designated Na-GST-1, Na-GST-2, and Na-GST-3, respectively) were isolated from cDNA based on their sequence similarity to Ac-GST-1, a GST from the dog hookworm Ancylostoma caninum. The open reading frames of the three N. americanus GSTs each contain 206 amino acids with 51% to 69% sequence identity between each other and Ac-GST-1. Sequence alignment with GSTs from other organisms shows that the three Na-GSTs belong to a nematode-specific nu-class GST family. All three Na-GSTs, when expressed in Pichia pastoris, exhibited low lipid peroxidase and glutathione-conjugating enzymatic activities but high heme-binding capacities, and they may be involved in the detoxification and/or transport of heme. In two separate vaccine trials, recombinant Na-GST-1 formulated with Alhydrogel elicited 32 and 39% reductions in adult hookworm burdens (P < 0.05) following N. americanus larval challenge relative to the results for a group immunized with Alhydrogel alone. In contrast, no protection was observed in vaccine trials with Na-GST-2 or Na-GST-3. On the basis of these and other preclinical data, Na-GST-1 is under possible consideration for further vaccine development.
AB - Hookworm glutathione S-transferases (GSTs) are critical for parasite blood feeding and survival and represent potential targets for vaccination. Three cDNAs, each encoding a full-length GST protein from the human hookworm Necator americanus (and designated Na-GST-1, Na-GST-2, and Na-GST-3, respectively) were isolated from cDNA based on their sequence similarity to Ac-GST-1, a GST from the dog hookworm Ancylostoma caninum. The open reading frames of the three N. americanus GSTs each contain 206 amino acids with 51% to 69% sequence identity between each other and Ac-GST-1. Sequence alignment with GSTs from other organisms shows that the three Na-GSTs belong to a nematode-specific nu-class GST family. All three Na-GSTs, when expressed in Pichia pastoris, exhibited low lipid peroxidase and glutathione-conjugating enzymatic activities but high heme-binding capacities, and they may be involved in the detoxification and/or transport of heme. In two separate vaccine trials, recombinant Na-GST-1 formulated with Alhydrogel elicited 32 and 39% reductions in adult hookworm burdens (P < 0.05) following N. americanus larval challenge relative to the results for a group immunized with Alhydrogel alone. In contrast, no protection was observed in vaccine trials with Na-GST-2 or Na-GST-3. On the basis of these and other preclinical data, Na-GST-1 is under possible consideration for further vaccine development.
U2 - 10.1128/IAI.00848-09
DO - 10.1128/IAI.00848-09
M3 - Article
C2 - 20145100
SN - 0019-9567
VL - 78
SP - 1552
EP - 1563
JO - Infection and Immunity
JF - Infection and Immunity
IS - 4
ER -
