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Improving the immunogenicity and protective efficacy of a whole-killed malaria blood-stage vaccine by chloroquine.
Parasite Immunology ( IF 2.2 ) Pub Date : 2019-11-11 , DOI: 10.1111/pim.12682
Yong Fu 1 , Xiao Lu 1 , Feng Zhu 1 , Yunxiang Zhao 1 , Yan Ding 1 , Lilin Ye 2 , Bo Guo 1 , Taiping Liu 1 , Wenyue Xu 1
Affiliation  

A whole-killed malaria blood-stage vaccine (WKV) is promising in reducing the morbidity and mortality of malaria patients, but its efficacy needs to be improved. We found that the antimalarial drug chloroquine could augment the protective efficacy of the WKV of Plasmodium yoelii. The direct antimalarial effect of chloroquine on parasites during immunization could be excluded, as the administration of chloroquine or chloroquine plus alum every two weeks had a slight effect on parasitemia, and an immunization with NP-KLH (4-hydroxy-3-nitrophenylacetyl Keyhole Limpet Hemocyanin) plus chloroquine could significantly promote the generation of NP-specific antibodies. Additionally, alum was required for chloroquine to augment the immunogenicity of the pRBC lysate. Chloroquine did not promote the parasite-specific CD4+ T-cell responses, but significantly enhanced the WKV-induced germinal centre B cell reactions, class-switch recombination and secretion of functionally protective antibodies to plasmodium. The elevated parasite-specific antibodies were demonstrated to largely contribute to the chloroquine-enhanced protective immunity. Thus, we report that chloroquine could be used as an adjuvant to enhance the protective immunity of WKVs through promoting humoral responses.

中文翻译:

通过氯喹提高全杀疟疾血期疫苗的免疫原性和保护功效。

一种全杀疟疾血液级疫苗(WKV)有望降低疟疾患者的发病率和死亡率,但其疗效有待提高。我们发现抗疟药氯喹可以增强约氏疟原虫WKV的保护功效。可以排除免疫过程中氯喹对寄生虫的直接抗疟作用,因为每两周施用一次氯喹或氯喹加明矾对寄生虫有轻微影响,并且用NP-KLH免疫(4-羟基-3-硝基苯基乙酰基匙孔hole)血蓝蛋白)加氯喹可以显着促进NP特异性抗体的产生。另外,氯喹需要明矾来增强pRBC裂解物的免疫原性。氯喹不促进寄生虫特异性CD4 + T细胞反应,但显着增强了WKV诱导的生发中心B细胞反应,类别转换重组以及针对疟原虫的功能性保护性抗体的分泌。高水平的寄生虫特异性抗体被证明在很大程度上增强了氯喹的保护性免疫力。因此,我们报道氯喹可以用作佐剂,通过促进体液反应来增强WKV的保护性免疫。
更新日期:2019-11-01
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