Genetic diversity and immunogenicity of the merozoite surface protein 1 C-terminal 19-kDa fragment of Plasmodium ovale imported from Africa into China.
Genetic diversity and immunogenicity of the merozoite surface protein 1 C-terminal 19-kDa fragment of Plasmodium ovale imported from Africa into China.
复制标题
从非洲进口到中国的卵形疟原虫裂殖子表面蛋白1 C端19-kDa片段的遗传多样性和免疫原性。
DOI：
10.1186/s13071-021-05086-6
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发表时间：
2021-11-24
影响因子：
3.2
通讯作者：
Cheng Y
中科院分区：
文献类型：
--
作者：
Xu Q;Liu S;Kassegne K;Yang B;Lu J;Sun Y;Zhong W;Zhang M;Liu Y;Zhu G;Cao J;Cheng Y
裂殖子表面蛋白1（MSP 1）在疟原虫侵入红细胞中起重要作用。MSP 1的C-末端19-kDa区域长期以来被认为是针对恶性疟原虫的疟疾血液阶段疫苗的主要候选抗原之一。然而，有关卵圆疟原虫MSP 1（PoMSP 119）C末端19-kDa区域的信息有限。本研究旨在分析PoMSP 119的遗传多样性和免疫原性。共使用了2012-2016年期间从非洲进口到中国的37株卵形疟原虫临床分离株，包括卵形疟原虫Curtisi和卵形疟原虫Wallikeri。使用基因组DNA通过聚合酶链反应扩增卵形毕赤酵母Curtisi（poc）msp 119（pocmsp 119）和卵形毕赤酵母Wallikeri（pow）msp 119（powmsp 119）基因。利用GeneDoc第6版程序分析了pomsp 119的遗传多样性。在大肠杆菌表达系统中表达重组PoMSP 119（rPoMSP 119）-谷胱甘肽S-转移酶（GST）蛋白，并通过western blot分析。用rPoMSP 119-GST免疫BALB/c小鼠，用酶联免疫吸附试验（ELISA）检测其免疫应答。此外，通过淋巴细胞增殖试验评估抗原特异性T细胞应答。共49份来自健康个体和感染卵形疟原虫的个体的血清样品用于通过使用蛋白质微阵列评估天然免疫应答。pomsp 119基因序列在所有临床分离株中完全保守。rPoMSP 119蛋白被高效表达并纯化为~ 37-kDa蛋白。用rPoMSP 119-GST免疫小鼠，观察到高抗体应答。rPoMSP 119-GST具有较高的亲合力指数，rPocMSP 119和rPowMSP 119的平均亲合力指数分别为92.57%和85.32%。观察到rPocMSP 119和rPowMSP 119之间存在交叉反应性。rPocMSP 119和rPowMSP 119免疫的小鼠脾细胞增殖试验中发现对rPocMSP 119（69.51%）和rPowMSP 119（52.17%）的细胞免疫应答。rPoMSP 119-GST蛋白检测卵形疟原虫感染者自然免疫应答的敏感性和特异性分别为89.96%和75%。本研究揭示了pomsp 119的高度保守的基因序列。此外，在卵形疟原虫感染中观察到针对rPoMSP 1的天然获得性体液免疫应答，并且还鉴定了rPoMSP 119在小鼠中的高免疫原性。这些具有指导意义的发现应该鼓励进一步测试PoMSP 119以进行合理的疫苗设计。在线版本包含补充材料，可通过10.1186/s13071-021-05086-6获得。
Merozoite surface protein 1 (MSP1) plays an essential role in erythrocyte invasion by malaria parasites. The C-terminal 19-kDa region of MSP1 has long been considered one of the major candidate antigens for a malaria blood-stage vaccine against Plasmodium falciparum. However, there is limited information on the C-terminal 19-kDa region of Plasmodium ovale MSP1 (PoMSP119). This study aims to analyze the genetic diversity and immunogenicity of PoMSP119. A total of 37 clinical Plasmodium ovale isolates including Plasmodium ovale curtisi and Plasmodium ovale wallikeri imported from Africa into China and collected during the period 2012–2016 were used. Genomic DNA was used to amplify P. ovale curtisi (poc) msp119 (pocmsp119) and P. ovale wallikeri (pow) msp119 (powmsp119) genes by polymerase chain reaction. The genetic diversity of pomsp119 was analyzed using the GeneDoc version 6 programs. Recombinant PoMSP119 (rPoMSP119)-glutathione S-transferase (GST) proteins were expressed in an Escherichia coli expression system and analyzed by western blot. Immune responses in BALB/c mice immunized with rPoMSP119-GST were determined using enzyme-linked immunosorbent assay. In addition, antigen-specific T cell responses were assessed by lymphocyte proliferation assays. A total of 49 serum samples from healthy individuals and individuals infected with P. ovale were used for the evaluation of natural immune responses by using protein microarrays. Sequences of pomsp119 were found to be thoroughly conserved in all the clinical isolates. rPoMSP119 proteins were efficiently expressed and purified as ~ 37-kDa proteins. High antibody responses in mice immunized with rPoMSP119-GST were observed. rPoMSP119-GST induced high avidity indexes, with an average of 92.57% and 85.32% for rPocMSP119 and rPowMSP119, respectively. Cross-reactivity between rPocMSP119 and rPowMSP119 was observed. Cellular immune responses to rPocMSP119 (69.51%) and rPowMSP119 (52.17%) induced in rPocMSP119- and rPowMSP119-immunized mice were found in the splenocyte proliferation assays. The sensitivity and specificity of rPoMSP119-GST proteins for the detection of natural immune responses in patients infected with P. ovale were 89.96% and 75%, respectively. This study revealed highly conserved gene sequences of pomsp119. In addition, naturally acquired humoral immune responses against rPoMSP1 were observed in P. ovale infections, and high immunogenicity of rPoMSP119 in mice was also identified. These instructive findings should encourage further testing of PoMSP119 for rational vaccine design. The online version contains supplementary material available at 10.1186/s13071-021-05086-6.
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影响因子：
9.3
作者：
Cutts JC;Powell R;Agius PA;Beeson JG;Simpson JA;Fowkes FJ
通讯作者：
Fowkes FJ
DOI：
10.1084/jem.186.10.1689
发表时间：
1997-11-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Guevara Patiño JA;Holder AA;McBride JS;Blackman MJ
通讯作者：
Blackman MJ
影响因子：
2.8
作者：
HOLDER, AA;BLACKMAN, MJ;SHAI, S
通讯作者：
SHAI, S
影响因子：
6.4
作者：
Egan, AF;Morris, J;Riley, EM
通讯作者：
Riley, EM
DOI：
10.1084/jem.172.1.379
发表时间：
1990-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Blackman MJ;Heidrich HG;Donachie S;McBride JS;Holder AA
通讯作者：
Holder AA