Improving the immunogenicity and protective efficacy of a whole-killed malaria blood-stage vaccine by chloroquine
Improving the immunogenicity and protective efficacy of a whole-killed malaria blood-stage vaccine by chloroquine
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氯喹提高全灭活疟疾血期疫苗的免疫原性和保护功效
DOI：
10.1111/pim.12682
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发表时间：
2020
影响因子：
2.2
通讯作者：
Xu Wenyue
中科院分区：
文献类型：
--
作者：
Fu Yong;Lu Xiao;Zhu Feng;Zhao Yunxiang;Ding Yan;Ye Lilin;Guo Bo;Liu Taiping;Xu Wenyue
全灭活疟疾血液期疫苗（WKV）有望降低疟疾患者的发病率和死亡率，但其有效性有待提高。我们发现抗疟药氯喹可增强约氏疟原虫WKV的保护效力。可以排除氯喹在免疫过程中对寄生虫的直接抗疟作用，因为每两周给予氯喹或氯喹加明矾对寄生虫血症有轻微影响，并且用NP-KLH（4-羟基-3-硝基苯乙酰基钥孔血蓝蛋白）加氯喹免疫可以显著促进NP特异性抗体的产生。此外，氯喹需要明矾以增强pRBC裂解物的免疫原性。氯喹不促进疟原虫特异性CD4 + T细胞反应，但显著增强WKV诱导的生发中心B细胞反应、类转换重组和疟原虫功能保护性抗体的分泌。已证明寄生虫特异性抗体升高在很大程度上有助于氯喹增强保护性免疫。因此，我们报告氯喹可以作为佐剂，以提高WKV的保护性免疫，通过促进体液反应。
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 ofPlasmodium 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 toplasmodium. 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.