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对抗河盲症的疫苗:在小鼠模型中针对盘尾丝虫感染的疫苗的表达、筛选及配方

Vaccines to combat river blindness: expression, selection and formulation of vaccines against infection with Onchocerca volvulus in a mouse model.

作者信息

Hess Jessica A, Zhan Bin, Bonne-Année Sandra, Deckman Jessica M, Bottazzi Maria Elena, Hotez Peter J, Klei Thomas R, Lustigman Sara, Abraham David

机构信息

Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, 233 S. 10th Street, Philadelphia, PA 19107, USA.

Department of Pediatrics, National School of Tropical Medicine, Baylor College of Medicine,, Houston, TX 77030, USA; Sabin Vaccine Institute and Texas Children's Hospital Center for Vaccine Development, 1102 Bates St, Ste. 550, Houston, TX 77030, USA.

出版信息

Int J Parasitol. 2014 Aug;44(9):637-46. doi: 10.1016/j.ijpara.2014.04.006. Epub 2014 Jun 5.

Abstract

Human onchocerciasis is a neglected tropical disease caused by Onchocerca volvulus and an important cause of blindness and chronic disability in the developing world. Although mass drug administration of ivermectin has had a profound effect on control of the disease, additional tools are critically needed including the need for a vaccine against onchocerciasis. The objectives of the present study were to: (i) select antigens with known vaccine pedigrees as components of a vaccine; (ii) produce the selected vaccine antigens under controlled conditions, using two expression systems and in one laboratory and (iii) evaluate their vaccine efficacy using a single immunisation protocol in mice. In addition, we tested the hypothesis that joining protective antigens as a fusion protein or in combination, into a multivalent vaccine, would improve the ability of the vaccine to induce protective immunity. Out of eight vaccine candidates tested in this study, Ov-103, Ov-RAL-2 and Ov-CPI-2M were shown to reproducibly induce protective immunity when administered individually, as fusion proteins or in combination. Although there was no increase in the level of protective immunity induced by combining the antigens into one vaccine, these antigens remain strong candidates for inclusion in a vaccine to control onchocerciasis in humans.

摘要

人类盘尾丝虫病是一种由盘尾丝虫引起的被忽视的热带疾病,是发展中世界失明和慢性残疾的一个重要原因。尽管大规模使用伊维菌素进行药物治疗对该疾病的控制产生了深远影响,但仍迫切需要其他工具,包括需要一种针对盘尾丝虫病的疫苗。本研究的目的是:(i)选择具有已知疫苗谱系的抗原作为疫苗成分;(ii)在一个实验室中使用两种表达系统在受控条件下生产所选的疫苗抗原;(iii)在小鼠中使用单一免疫方案评估其疫苗效力。此外,我们还测试了以下假设:将保护性抗原作为融合蛋白或组合加入多价疫苗中,将提高疫苗诱导保护性免疫的能力。在本研究测试的八种候选疫苗中,Ov-103、Ov-RAL-2和Ov-CPI-2M单独给药、作为融合蛋白给药或联合给药时,均显示可重复诱导保护性免疫。尽管将这些抗原组合成一种疫苗诱导的保护性免疫水平没有提高,但这些抗原仍是用于控制人类盘尾丝虫病疫苗的有力候选者。

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