Plug and play virus-like particles for the generation of anti-toxin antibodies

IF 3.6 Q2 TOXICOLOGY Toxicon: X Pub Date : 2024-09-01 DOI:10.1016/j.toxcx.2024.100204
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Abstract

Snakebite is a major global health concern, for which antivenom remains the only approved treatment to neutralise the harmful effects of the toxins. However, some medically important toxins are poorly immunogenic, resulting in reduced efficacy of the final product. Boosting the immunogenicity of these toxins in the commercial antivenom immunising mixtures could be an effective strategy to improve the final dose efficacy, and displaying snake antigens on Virus-like particles (VLPs) is one method for this. However, despite some applications in the field of snakebite, VLPs have yet to be explored in methods that could be practical at an antivenom manufacturing scale. Here we describe the utilisation of a “plug and play” VLP system to display immunogenic linear peptide epitopes from three finger toxins (3FTxs) and generate anti-toxin antibodies. Rabbits were immunised with VLPs displaying individual consensus linear epitopes and their antibody responses were characterised by immunoassay. Of the three experimental consensus sequences, two produced antibodies capable of recognising the consensus peptides, whilst only one of these could also recognise native whole toxins. Further characterisation of antibodies raised against this peptide demonstrated a sub-class specific response, and that these were able to elicit partially neutralising antibody responses, resulting in increased survival times in a murine snakebite envenoming model.

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用于生成抗毒素抗体的即插即用病毒样颗粒
毒蛇咬伤是全球关注的主要健康问题,抗蛇毒血清仍是唯一获准用于中和毒素有害影响的治疗方法。然而,一些在医学上很重要的毒素免疫原性很差,导致最终产品的疗效降低。在商用抗蛇毒血清免疫混合物中增强这些毒素的免疫原性,可能是提高最终剂量疗效的有效策略,而在病毒样颗粒(VLPs)上显示蛇类抗原则是其中一种方法。然而,尽管在蛇咬伤领域有一些应用,VLPs 仍有待于在抗蛇毒血清生产规模的实用方法中进行探索。在这里,我们介绍了利用 "即插即用 "VLP系统来显示三指毒素(3FTx)的免疫原线性肽表位并产生抗毒素抗体的方法。用显示单个共识线性表位的 VLP 对兔子进行免疫,并用免疫测定法鉴定兔子的抗体反应。在三个实验性共识序列中,有两个产生的抗体能够识别共识肽,而其中只有一个还能识别原生的整个毒素。对针对这种多肽产生的抗体进行的进一步鉴定表明,这种抗体具有亚类特异性反应,能够引起部分中和抗体反应,从而延长小鼠蛇咬伤模型的存活时间。
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来源期刊
Toxicon: X
Toxicon: X Pharmacology, Toxicology and Pharmaceutics-Toxicology
CiteScore
6.50
自引率
0.00%
发文量
33
审稿时长
14 weeks
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