Geographical and temporal conservation of antibody recognition of Plasmodium falciparum 2 variant surface antigens
Geographical and temporal conservation of antibody recognition of Plasmodium falciparum 2 variant surface antigens
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DOI：
10.1128/iai.72.6.3531-3535.2004
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发表时间：
2004-06-01
影响因子：
3.1
通讯作者：
Hviid, L
中科院分区：
文献类型：
--
作者：
Nielsen, MA;Vestergaard, LS;Hviid, L
对恶性疟疾的保护作用缓慢，可能反映了重要抗原的广泛多样性。介导寄生虫与一系列宿主分子黏附的变异型表面抗原(VSA)被认为是获得性保护性免疫的重要靶点，但它们的多样性使它们成为可疑的疫苗候选。我们测定了在四个地理位置遥远和流行病学不同的地点采集的人血浆中VSA特异性免疫球蛋白G(Ig G)的水平，该水平对来自三个非洲国家的恶性疟原虫分离株表达的VSA具有特异性。识别单个寄生虫分离株的VSA特异性免疫球蛋白的血浆水平取决于血浆采集地点的传播强度，但在很大程度上与寄生虫的地理来源无关。因此，免疫上不同的VSA的全部谱系似乎是有限的，并且在地理上是保守的，很可能是由于功能限制。此外，血浆样本经常对10年后分离的寄生虫表达的VSA具有较高的免疫球蛋白反应性，这表明该谱系也是暂时稳定的。来自严重疟疾患者的寄生虫表达的VSA(VSA(SM))比其他寄生虫表达的VSA(SM)更容易被血浆免疫球蛋白识别，但更重要的是，VSA(SM)型抗原似乎也表现出很大的抗原同质性。我们的发现是，免疫上不同的VSA，特别是VSA(SM)的谱系在地理和时间上是保守的，这为开发基于VSA的疫苗的可行性带来了希望，该疫苗专门设计用于加速自然获得性免疫，从而加强对严重和危及生命的恶性疟疾的保护。
The slow acquisition of protection against Plasmodium falciparum malaria probably reflects the extensive diversity of important antigens. The variant surface antigens (VSA) that mediate parasite adhesion to a range of host molecules are regarded as important targets of acquired protective immunity, but their diversity makes them questionable vaccine candidates. We determined levels of VSA-specific immunoglobulin G (IgG) in human plasma collected at four geographically distant and epidemiologically distinct localities with specificity for VSA expressed by P. falciparum isolates from three African countries. Plasma levels of VSA-specific IgG recognizing individual parasite isolates depended on the transmission intensity at the site of plasma collection but were largely independent of the geographical origin of the parasites. The total repertoire of immunologically distinct VSA thus appears to be finite and geographically conserved, most likely due to functional constraints. Furthermore, plasma samples frequently had high IgG reactivity to VSA expressed by parasites isolated more than 10 years later, showing that the repertoire is also temporally stable. Parasites from patients with severe malaria expressed VSA (VSA(SM)) that were better recognized by plasma IgG than VSA expressed by other parasites, but importantly, VSA(SM)-type antigens also appeared to show substantial antigenic homogeneity. Our finding that the repertoire of immunologically distinct VSA in general, and in particular that of VSA(SM), is geographically and temporally conserved raises hopes for the feasibility of developing VSA-based vaccines specifically designed to accelerate naturally acquired immunity, thereby enhancing protection against severe and life-threatening P. falciparum malaria.