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诱导和补体固定抗体对恶性疟原虫裂殖子表面蛋白 3α的动力学与免疫球蛋白 G 亚类和免疫球蛋白 M 的关系。

Induction and Kinetics of Complement-Fixing Antibodies Against Plasmodium vivax Merozoite Surface Protein 3α and Relationship With Immunoglobulin G Subclasses and Immunoglobulin M.

机构信息

Menzies School of Health Research, Darwin, Australia.

Charles Darwin University, Darwin, Australia.

出版信息

J Infect Dis. 2019 Nov 6;220(12):1950-1961. doi: 10.1093/infdis/jiz407.

Abstract

BACKGROUND

Complement-fixing antibodies are important mediators of protection against Plasmodium falciparum malaria. However, complement-fixing antibodies remain uncharacterized for Plasmodium vivax malaria. P. vivax merozoite surface protein 3α (PvMSP3α) is a target of acquired immunity and a potential vaccine candidate.

METHODS

Plasma from children and adults with P. vivax malaria in Sabah, Malaysia, were collected during acute infection, 7 and 28 days after drug treatment. Complement-fixing antibodies and immunoglobulin M and G (IgM and IgG), targeting 3 distinctive regions of PvMSP3α, were measured by means of enzyme-linked immunosorbent assay.

RESULTS

The seroprevalence of complement-fixing antibodies was highest against the PvMSP3α central region (77.6%). IgG1, IgG3, and IgM were significantly correlated with C1q fixation, and both purified IgG and IgM were capable of mediating C1q fixation to PvMSP3α. Complement-fixing antibody levels were similar between age groups, but IgM was predominant in children and IgG3 more prevalent in adults. Levels of functional antibodies increased after acute infection through 7 days after treatment but rapidly waned by day 28.

CONCLUSION

Our study demonstrates that PvMSP3α antibodies acquired during P. vivax infection can mediate complement fixation and shows the important influence of age in shaping these specific antibody responses. Further studies are warranted to understand the role of these functional antibodies in protective immunity against P. vivax malaria.

摘要

背景

补体结合抗体是抵御恶性疟原虫疟疾的重要保护介质。然而,针对间日疟原虫疟疾的补体结合抗体仍未得到充分描述。间日疟原虫裂殖体表面蛋白 3α(PvMSP3α)是获得性免疫的靶标,也是一种有潜力的疫苗候选物。

方法

在马来西亚沙巴州,于儿童和成人急性感染期间以及药物治疗后 7 天和 28 天采集间日疟原虫疟疾患者的血浆。通过酶联免疫吸附试验测定针对 PvMSP3α 的 3 个不同区域的补体结合抗体和免疫球蛋白 M 和 G(IgM 和 IgG)。

结果

针对 PvMSP3α 中心区域的补体结合抗体的血清阳性率最高(77.6%)。IgG1、IgG3 和 IgM 与 C1q 固定呈显著相关,纯化的 IgG 和 IgM 均能够介导 C1q 对 PvMSP3α 的固定。补体结合抗体水平在年龄组之间相似,但 IgM 在儿童中更为常见,而 IgG3 在成人中更为常见。在急性感染后通过治疗第 7 天,功能性抗体水平增加,但在第 28 天迅速下降。

结论

我们的研究表明,间日疟原虫感染期间获得的 PvMSP3α 抗体能够介导补体固定,并表明年龄对形成这些特异性抗体反应的重要影响。需要进一步研究以了解这些功能性抗体在抵抗间日疟原虫疟疾中的保护作用。

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