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用基于 MSP1 的制剂免疫小鼠并用表达 MSP1 的虫株进行攻毒,可诱导产生保护免疫。

Protective Immunity in Mice Immunized With MSP1-Based Formulations and Challenged With Expressing MSP1.

机构信息

Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.

Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.

出版信息

Front Immunol. 2020 Feb 19;11:28. doi: 10.3389/fimmu.2020.00028. eCollection 2020.

Abstract

The lack of continuous cultures has been an obstacle delaying pre-clinical testing of vaccine formulations based on known antigens. In this study, we generated a model to test available formulations based on the MSP1 antigen. The strains ANKA and NK65 were modified to express MSP1 instead of the endogenous MSP1. The hybrid parasites were used to challenge C57BL/6 or BALB/c mice immunized with MSP1-based vaccine formulations. The MSP1 was correctly expressed in the hybrid mutant lines as confirmed by immunofluorescence using anti-MSP1 monoclonal antibodies and by Western blot. Replacement of the MSP1 by the MSP1 had no impact on asexual growth . High titers of specific antibodies to MSP1 were not sufficient to control initial parasitemia in the immunized mice, but late parasitemia control and a balanced inflammatory process protected these mice from dying, suggesting that an established immune response to MSP1 in this model can help immunity mounted later during infection.

摘要

缺乏连续培养一直是阻碍基于已知抗原的疫苗制剂进行临床前测试的一个障碍。在这项研究中,我们构建了一个模型来测试基于 MSP1 抗原的现有制剂。将 ANKA 和 NK65 株系修饰为表达 MSP1 而不是内源性 MSP1。用杂交寄生虫对用 MSP1 为基础的疫苗制剂免疫的 C57BL/6 或 BALB/c 小鼠进行挑战。通过用抗 MSP1 单克隆抗体进行免疫荧光和 Western blot 证实,MSP1 在杂交突变株系中正确表达。用 MSP1 替换 MSP1 对无性繁殖没有影响。针对 MSP1 的高滴度特异性抗体不足以控制免疫小鼠的初始寄生虫血症,但晚期寄生虫血症控制和平衡的炎症过程使这些小鼠免于死亡,表明在该模型中对 MSP1 的既定免疫反应可以帮助在感染后期产生的免疫。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93be/7045055/958b8b38a21d/fimmu-11-00028-g0001.jpg

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