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基于与腮腺炎核衣壳蛋白融合的环子孢子蛋白的小鼠疟疾保护疫苗。

Protective Malaria Vaccine in Mice Based on the Circumsporozoite Protein Fused with the Mumps Nucleocapsid Protein.

作者信息

Marques Rodolfo F, Gimenez Alba Marina, Aliprandini Eduardo, Novais Janaina T, Cury Diego P, Watanabe Ii-Sei, Dominguez Mariana R, Silveira Eduardo L V, Amino Rogerio, Soares Irene S

机构信息

Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508-000 SP, Brazil.

Center of Cellular and Molecular Therapy, Federal University of São Paulo, São Paulo 04044-010 SP, Brazil.

出版信息

Vaccines (Basel). 2020 Apr 19;8(2):190. doi: 10.3390/vaccines8020190.

Abstract

is the most common species of human malaria parasite found outside Africa, with high endemicity in Asia, Central and South America, and Oceania. Although causes the majority of deaths, can lead to severe malaria and result in significant morbidity and mortality. The development of a protective vaccine will be a major step toward malaria elimination. Recently, a formulation containing the three allelic variants of the circumsporozoite protein (PvCSP-All epitopes) showed partial protection in mice after a challenge with the hybrid (Pb) sporozoite, in which the PbCSP central repeats were replaced by the VK210 PvCSP repeats (Pb/Pv sporozoite). In the present study, the chimeric PvCSP allelic variants (VK210, VK247, and -like) were fused with the mumps virus nucleocapsid protein in the absence (NLP-CSP) or presence of the conserved C-terminal (CT) domain of PvCSP (NLP-CSP). To elicit stronger humoral and cellular responses, yeast was used to assemble them as nucleocapsid-like particles (NLPs). Mice were immunized with each recombinant protein adjuvanted with Poly (I:C) and presented a high frequency of antigen-specific antibody-secreting cells (ASCs) on days 5 and 30, respectively, in the spleen and bone marrow. Moreover, high IgG titers against all PvCSP variants were detected in the sera. Later, these immunized mice with NLP-CSP were challenged with Pb/Pv sporozoites. Sterile protection was observed in 30% of the challenged mice. Therefore, this vaccine formulation use has the potential to be a good candidate for the development of a universal vaccine against malaria.

摘要

是在非洲以外发现的最常见的人类疟原虫物种,在亚洲、中美洲、南美洲和大洋洲具有高度地方性。虽然导致大多数死亡,但也可导致严重疟疾并造成显著的发病和死亡。开发一种保护性疫苗将是朝着消除疟疾迈出的重要一步。最近,一种含有环子孢子蛋白(PvCSP)三个等位基因变体(PvCSP-所有表位)的制剂在用杂交疟原虫(Pb)子孢子攻击后在小鼠中显示出部分保护作用,其中PbCSP中央重复序列被VK210 PvCSP重复序列取代(Pb/Pv子孢子)。在本研究中,嵌合PvCSP等位基因变体(VK210、VK247和类似物)在不存在(NLP-CSP)或存在PvCSP保守C末端(CT)结构域(NLP-CSP)的情况下与腮腺炎病毒核衣壳蛋白融合。为了引发更强的体液和细胞反应,使用酵母将它们组装成核衣壳样颗粒(NLPs)。用聚(I:C)佐剂的每种重组蛋白免疫小鼠,分别在第5天和第30天在脾脏和骨髓中呈现出高频率的抗原特异性抗体分泌细胞(ASCs)。此外,在血清中检测到针对所有PvCSP变体的高IgG滴度。后来,用Pb/Pv子孢子攻击这些用NLP-CSP免疫的小鼠。在30%的受攻击小鼠中观察到无菌保护。因此,这种疫苗制剂有可能成为开发针对疟疾的通用疫苗的良好候选者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f52d/7348950/558e4146bb5b/vaccines-08-00190-g001a.jpg

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