In:
Infection and Immunity, American Society for Microbiology, Vol. 78, No. 4 ( 2010-04), p. 1552-1563
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 Pi chia 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.
Type of Medium:
Online Resource
ISSN:
0019-9567
,
1098-5522
DOI:
10.1128/IAI.00848-09
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2010
detail.hit.zdb_id:
1483247-1
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