Molecular cloning, biochemical characterization, and partial protective immunity of the heme-binding glutathione S-transferases from the human hookworm Necator americanus

Zhan, Bin, Perally, Samirah, Brophy, Peter M., Xue, Jian, Goud, Gaddam, Liu, Sen, Deumic, Vehid, de Oliveira, Luciana M., Bethony, Jeffrey, Bottazzi, Maria Elena, Jiang, Desheng, Gillespie, Portia, Xiao, Shu-hua, Gupta, Richi, Loukas, Alex, Ranjit, Najju, Lustigman, Sara, Oksov, Yelena, and Hotez, Peter (2010) Molecular cloning, biochemical characterization, and partial protective immunity of the heme-binding glutathione S-transferases from the human hookworm Necator americanus. Infection and Immunity, 78 (4). pp. 1552-1563.

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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.

Item ID: 28669
Item Type: Article (Research - C1)
ISSN: 1098-5522
Keywords: aluminum hydroxide; amino acid; glutathione transferase; heme; lipid peroxidase; vaccine; adjuvant therapy; amino acid sequence; article; biochemistry; controlled study; detoxification; enzyme activity; glutathione metabolism; hookworm; immunity; molecular cloning; Necator americanus; nematode; nonhuman; nucleotide sequence; open reading frame; organism; Pichia pastoris; priority journal; protein expression; sequence alignment; statistical significance; adjuvants, immunologic; aluminum hydroxide; amino acid sequence; animals; antigens, helminth; cloning, molecular; cricetinae; DNA, complementary; DNA, helminth; gene expression; glutathione; glutathione transferase; heme; humans; lipid peroxidation; molecular sequence data; Necator americanus; necatoriasis; open reading frames; pichia; recombinant proteins; sequence alignment; sequence homology; amino acid; vaccines; subunit
Date Deposited: 19 Aug 2013 02:44
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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