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抗疟疫苗候选修饰肽混合物(IMPIPS)在小鼠模型中的安全性和免疫原性初步评估。

Preliminary Evaluation of the Safety and Immunogenicity of an Antimalarial Vaccine Candidate Modified Peptide (IMPIPS) Mixture in a Murine Model.

机构信息

Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia.

Master's Programme in Biochemistry, Medical School, Universidad Nacional de Colombia, Bogotá, Colombia.

出版信息

J Immunol Res. 2019 Dec 30;2019:3832513. doi: 10.1155/2019/3832513. eCollection 2019.

Abstract

Malaria continues being a high-impact disease regarding public health worldwide; the WHO report for malaria in 2018 estimated that ~219 million cases occurred in 2017, mostly caused by the parasite . The disease cost the lives of more than 400,000 people, mainly in Africa. In spite of great efforts aimed at developing better prevention (i.e., a highly effective vaccine), diagnosis, and treatment methods for malaria, no efficient solution to this disease has been advanced to date. The Fundación Instituto de Inmunología de Colombia (FIDIC) has been developing studies aimed at furthering the search for vaccine candidates for controlling malaria. However, vaccine development involves safety and immunogenicity studies regarding their formulation in animal models before proceeding to clinical studies. The present work has thus been aimed at evaluating the safety and immunogenicity of a mixture of 23 chemically synthesised, modified peptides (immune protection-inducing protein structure (IMPIPS)) derived from different proteins. Single and repeat dose assays were thus used with male and female BALB/c mice which were immunised with the IMPIPS mixture. It was found that single and repeat dose immunisation with the IMPIPS mixture was safe, both locally and systemically. It was observed that the antibodies so stimulated recognised the parasite's native proteins and inhibited merozoite invasion of red blood cells when evaluating the humoral immune response induced by the IMPIPS mixture. Such results suggested that the IMPIPS peptide mixture could be a safe candidate to be tested during the next stage involved in developing an antimalarial vaccine, evaluating local safety, immunogenicity, and protection in a nonhuman primate model.

摘要

疟疾仍然是全球公共卫生的一个重大影响疾病;世界卫生组织(WHO)2018 年的疟疾报告估计,2017 年有~2.19 亿例疟疾病例,主要由寄生虫引起。该疾病导致超过 40 万人死亡,主要在非洲。尽管为开发更好的疟疾预防(即高效疫苗)、诊断和治疗方法做出了巨大努力,但迄今为止,尚未提出针对该疾病的有效解决方案。哥伦比亚免疫研究所基金会(FIDIC)一直在开展研究,旨在进一步寻找控制疟疾的疫苗候选物。然而,疫苗开发涉及在动物模型中进行安全性和免疫原性研究,然后才能进行临床研究。因此,本工作旨在评估源自不同蛋白质的 23 种化学合成、修饰肽(免疫保护诱导蛋白结构(IMPIPS))混合物的安全性和免疫原性。使用雄性和雌性 BALB/c 小鼠进行单次和重复剂量试验,用 IMPIPS 混合物免疫这些小鼠。结果发现,单次和重复剂量免疫 IMPIPS 混合物是安全的,无论是局部还是全身。观察到,当评估 IMPIPS 混合物诱导的体液免疫反应时,如此刺激产生的抗体识别寄生虫的天然蛋白并抑制裂殖体入侵红细胞。这些结果表明,IMPIPS 肽混合物可能是一种安全的候选物,可以在开发抗疟疫苗的下一阶段进行测试,评估在非人类灵长类动物模型中的局部安全性、免疫原性和保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85fe/7012257/07d988d0f9d0/JIR2019-3832513.001.jpg

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