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编码兼性蛋白盘尾丝虫甘油醛-3-磷酸脱氢酶(Ov-GAPDH)的DNA疫苗在人类丝虫病小鼠模型中产生了部分保护作用。

DNA vaccine encoding the moonlighting protein Onchocerca volvulus glyceraldehyde-3-phosphate dehydrogenase (Ov-GAPDH) leads to partial protection in a mouse model of human filariasis.

作者信息

Steisslinger Vera, Korten Simone, Brattig Norbert W, Erttmann Klaus D

机构信息

Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Str. 74, D-20359 Hamburg, Germany.

Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Str. 74, D-20359 Hamburg, Germany; Department of Infection Medicine, Laboratory Lademannbogen Medical Service Center GmbH (Sonic Healthcare Group), Lademannbogen 61-63, D-22339 Hamburg, Germany.

出版信息

Vaccine. 2015 Oct 26;33(43):5861-5867. doi: 10.1016/j.vaccine.2015.07.110. Epub 2015 Aug 29.

Abstract

River blindness, caused by the filarial parasite Onchocerca volvulus, is a major socio-economic and public health problem in Sub-Saharan Africa. In January 2015, The Onchocerciasis Vaccine for Africa (TOVA) Initiative has been launched with the aim of providing new tools to complement mass drug administration (MDA) of ivermectin, thereby promoting elimination of onchocerciasis in Africa. In this context we here present Onchocerca volvulus glyceraldehyde-3-phosphate dehydrogenase (Ov-GAPDH) as a possible DNA vaccine candidate. We report that in a laboratory model for filariasis, immunization with Ov-GAPDH led to a significant reduction of adult worm load and microfilaraemia in BALB/c mice after challenge infection with the filarial parasite Litomosoides sigmodontis. Mice were either vaccinated with Ov-GAPDH.DNA plasmid (Ov-pGAPDH.DNA) alone or in combination with recombinantly expressed Ov-GAPDH protein (Ov-rGAPDH). During the following challenge infection of immunized and control mice with L. sigmodontis, those formulations which included the DNA plasmid, led to a significant reduction of adult worm loads (up to 57% median reduction) and microfilaraemia (up to 94% reduction) in immunized animals. In a further experiment, immunization with a mixture of four overlapping, synthetic Ov-GAPDH peptides (Ov-GAPDHpept), with alum as adjuvant, did not significantly reduce worm loads. Our results indicate that DNA vaccination with Ov-GAPDH has protective potential against filarial challenge infection in the mouse model. This suggests a transfer of the approach into the cattle Onchocerca ochengi model, where it is possible to investigate the effects of this vaccination in the context of a natural host-parasite relationship.

摘要

河盲症由丝状寄生虫盘尾丝虫引起,是撒哈拉以南非洲地区的一个主要社会经济和公共卫生问题。2015年1月,启动了非洲盘尾丝虫病疫苗(TOVA)倡议,旨在提供新工具以补充伊维菌素大规模药物给药(MDA),从而推动在非洲消除盘尾丝虫病。在此背景下,我们在此展示盘尾丝虫甘油醛-3-磷酸脱氢酶(Ov-GAPDH)作为一种可能的DNA疫苗候选物。我们报告称,在丝虫病实验室模型中,用Ov-GAPDH免疫导致在用丝状寄生虫冈比亚丝虫进行攻击感染后,BALB/c小鼠体内的成虫负荷和微丝蚴血症显著降低。小鼠单独接种Ov-GAPDH.DNA质粒(Ov-pGAPDH.DNA)或与重组表达的Ov-GAPDH蛋白(Ov-rGAPDH)联合接种。在随后用冈比亚丝虫对免疫小鼠和对照小鼠进行攻击感染期间,那些包含DNA质粒的制剂导致免疫动物体内的成虫负荷显著降低(中位数降低高达57%)和微丝蚴血症显著降低(降低高达94%)。在进一步的实验中,用四种重叠的合成Ov-GAPDH肽(Ov-GAPDHpept)与明矾作为佐剂的混合物进行免疫,并未显著降低虫负荷。我们的结果表明,用Ov-GAPDH进行DNA疫苗接种在小鼠模型中对丝状攻击感染具有保护潜力。这表明可将该方法应用于牛奥氏丝虫模型,在该模型中可以在自然宿主-寄生虫关系的背景下研究这种疫苗接种的效果。

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