Molecular Cloning, Biochemical Characterization, and Partial Protective Immunity of the Heme-Binding Glutathione S-Transferases from the Human Hookworm Necator americanus

Bin Zhan, Samirah Perally, Peter M. Brophy, Jian Xue, Gaddam Goud, Sen Liu, Vehid Deumic, Luciana de Oliveira, Jeffrey Bethony, Maria Elena Bottazzi, Desheng Jiang, Portia Gillespie, Shu-hua Xiao, Richi Gupta, Alex Loukas, Najju Ranjit, Sara Lustigman, Peter Hotez, Yelena Oksov

Research output: Contribution to journalArticlepeer-review

80 Citations (SciVal)

Abstract

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.
Original languageEnglish
Pages (from-to)1552-1563
Number of pages12
JournalInfection and Immunity
Volume78
Issue number4
DOIs
Publication statusPublished - Apr 2010

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