抗恶性疟原虫裂殖子表面蛋白 3γ（PvMSP3γ）抗体在自然感染时产生。

Anti-Plasmodium vivax merozoite surface protein 3 ϒ (PvMSP3 ϒ) antibodies upon natural infection.

机构信息

Molecular Biology of Malaria and Opportunistic Parasites Research Unit, Department of Parasitology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Department of Infectious Diseases, Tokai University School of Medicine, Isehara, Kanagawa, Japan.

出版信息

Sci Rep. 2024 Apr 26;14(1):9595. doi: 10.1038/s41598-024-59153-w.

DOI:10.1038/s41598-024-59153-w

PMID:38671033

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11053162/

Abstract

Merozoite surface protein 3 of Plasmodium vivax (PvMSP3) contains a repertoire of protein members with unique sequence organization. While the biological functions of these proteins await elucidation, PvMSP3 has been suggested to be potential vaccine targets. To date, studies on natural immune responses to this protein family have been confined to two members, PvMSP3α and PvMSP3β. This study analyzed natural IgG antibody responses to PvMSP3γ recombinant proteins derived from two variants: one containing insert blocks (CT1230nF) and the other without insert domain (NR25nF). The former variant was also expressed as two subfragment proteins: one encompassing variable domain I and insert block A (CT1230N) and the other spanning from insert block B to conserved block III (CT1230C). Serum samples were obtained from 246 symptomatic vivax malaria patients in Tak (n = 50) and Ubon Ratchathani (n = 196) Provinces. In total, 176 (71.5%) patients could mount antibodies to at least one recombinant PvMSP3γ antigen. IgG antibodies directed against antigens CT1230nF, CT1230N, CT1230C and NR25nF occurred in 96.6%, 61.4%, 71.6% and 68.2% of samples, respectively, suggesting the widespread occurrence of B-cell epitopes across PvMSP3γ. The rates of seropositivity seemed to correlate with the number of previous malaria episodes. Isotype analysis of anti-PvMSP3γ antibodies has shown predominant cytophilic subclass responses, accounting for 75.4-81.7% for IgG1 and 63.6-77.5% for IgG3. Comparing with previous studies in the same cohort, the numbers of serum samples reactive to antigens derived from P. vivax merozoite surface protein 9 (PvMSP9) and thrombospondin-related anonymous protein (PvTRAP) were higher than those to PvMSP3γ, being 92.7% and 87.0% versus 71.5%, respectively. Three (1.22%) serum samples were nonresponsive to all these malarial proteins. Nevertheless, the relevance of naturally acquired antibodies to PvMSP3γ in host protection requires further studies.

摘要

恶性疟原虫表面蛋白 3（PvMSP3）的裂殖子表面蛋白包含一组具有独特序列组织的蛋白成员。虽然这些蛋白质的生物学功能仍有待阐明，但 PvMSP3 被认为是潜在的疫苗靶点。迄今为止，对该蛋白家族的天然免疫反应的研究仅限于两个成员，PvMSP3α 和 PvMSP3β。本研究分析了来自两种变体的 PvMSP3γ 重组蛋白的天然 IgG 抗体反应：一种变体包含插入块（CT1230nF），另一种变体不含插入结构域（NR25nF）。前者还表达为两个亚片段蛋白：一个包含可变结构域 I 和插入块 A（CT1230N），另一个从插入块 B 延伸到保守块 III（CT1230C）。从达府（n=50）和乌汶叻差他尼府（n=196）的 246 例有症状的间日疟原虫疟疾患者中获得血清样本。总共有 176 例（71.5%）患者至少能对一种重组 PvMSP3γ 抗原产生抗体。针对 CT1230nF、CT1230N、CT1230C 和 NR25nF 抗原的 IgG 抗体分别在 96.6%、61.4%、71.6%和 68.2%的样本中出现，表明 PvMSP3γ 广泛存在 B 细胞表位。血清阳性率似乎与既往疟疾发作次数有关。抗-PvMSP3γ 抗体的同种型分析显示，亲细胞亚类反应占主导地位，IgG1 为 75.4-81.7%，IgG3 为 63.6-77.5%。与同一队列的先前研究相比，针对恶性疟原虫裂殖子表面蛋白 9（PvMSP9）和血栓反应蛋白相关未知蛋白（PvTRAP）来源抗原的血清样本数量高于针对 PvMSP3γ 的数量，分别为 92.7%和 87.0%与 71.5%。有 3 份（1.22%）血清样本对所有这些疟原虫蛋白均无反应。然而，天然获得的抗 PvMSP3γ 抗体在宿主保护中的相关性仍需进一步研究。