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

作者：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; Hotez Peter

来源：Infection and Immunity, 2010, 78(4): 1552-1563.

DOI：10.1128/IAI.00848-09

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.

• 出版日期2010-4
• 单位中国疾病预防控制中心寄生虫病预防控制所; 中国疾病预防控制中心; 河北医科大学