Comparison of naturally acquired antibody responses against the C-terminal processing products of Plasmodium vivax Merozoite Surface Protein-1 under low transmission and unstable malaria conditions in Sri Lanka

Comparison of naturally acquired antibody responses against the C-terminal processing products of Plasmodium vivax Merozoite Surface Protein-1 under low transmission and unstable malaria conditions in Sri Lanka
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DOI:
10.1016/j.ijpara.2006.09.002
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发表时间:
2007-02-01
影响因子:
4
通讯作者:
Udagama-Randeniya, Preethi V.
Udagama-Randeniya, Preethi V.
中科院分区:
医学2区
文献类型:
--
作者:
Wickramarachchi, Thilan;Illeperuma, Ruwan J.;Udagama-Randeniya, Preethi V.

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我们在此首次报告,通过 ELISA 分别使用 p42 和 p19 杆状病毒衍生的重组蛋白,对间日疟原虫裂殖子表面蛋白 1 的 42 和 19 kDa C 末端加工产物的自然获得抗体反应进行比较。测试人群包括经显微镜检查证实急性间日疟感染的患者,这些患者分别来自斯里兰卡的两个间日疟流行区(传播率低且疟疾状况不稳定)和非流行城市地区。在所有测试区域中,这两种蛋白的抗体流行率在个体和群体水平上对 p42 的反应往往比对 p19 的反应更大,其中 > 14% 的个体优先识别 p42,而对 p19 的识别率 < 2%。在以前没有接触过疟疾的患者中,21% 优先识别 p42,而没有人专门识别 p19。与非流行地区居民相比,流行地区居民的抗 p19 IgM 患病率显着降低,但抗 p42 IgM 患病率却没有显着降低。与抗 p42 IgM 相比,两个流行地区的个体产生的抗 p19 IgM 显着减少。 IgG1 是所有个体中两种抗原的主要 IgG 同种型。随着这两个流行地区接触疟疾的机会增加,抗 p19 抗体反应以功能重要的 IgG1 和 IgG3 同种型为主,同时 IgM 减少,而非流行地区居民所缺乏的。正如我们之前用相同的血清组报道的那样,PvAMA-1 也反映了这种抗体转换。相比之下,p42 的抗体转换仅限于接触范围更广的流行病居民。这些结果表明,流行病居民中针对 p42 多态性区域的以 IgM 为主的抗体反应可能会干扰以 IgG 为主的向 p19 的“保护性”同种型转变的发展,这可能会使疫苗的开发变得复杂。 (c) 2006 年澳大利亚寄生虫学协会。由 Elsevier Ltd 出版。保留所有权利。
We report here, for the first time, a comparison of naturally acquired antibody responses to the 42 and 19 kDa C-terminal processing products of Plasmodium vivax Merozoite Surface Protein-1 assayed by ELISA using p42 and p19 baculovirus-derived recombinant proteins, respectively. Test populations comprised patients with microscopy confirmed acute P. vivax infections from two regions endemic for vivax malaria where low transmission and unstable malaria conditions prevail, and a non-endemic urban area, in Sri Lanka. The antibody prevalence to the two proteins, both at the individual and population levels, tend to respond more to p42 than to p19 in all test areas, where > 14% of individuals preferentially recognized p42, compared with < 2% for p19. In patients with no previous exposure to malaria, 21% preferentially recognized p42, whereas none exclusively recognized p19. A significantly lower prevalence of anti-p19 IgM, but not anti-p42 IgM, was observed among residents from endemic areas compared with their non-endemic counterparts. Individuals from both endemic areas produced significantly less anti-p19 IgM compared with anti-p42 IgM. IgG1 was the predominant IgG isotype for both antigens in all individuals. With increasing exposure to malaria in both endemic areas, anti-p19 antibody responses were dominated by the functionally important IgG1 and IgG3 isotypes, with a concurrent reduction in IgM that was lacking in the non-endemic residents. This antibody switch was also reflected for PvAMA-1 as we previously reported with the identical battery of sera. In contrast, the antibody switch for p42 was restricted to endemic residents with more extensive exposure. These results suggest that an IgM-dominated antibody response against the p42 polymorphic region in endemic residents may interfere with the development of an IgG-dominated "protective" isotype shift to p19, that may complicate vaccine development. (c) 2006 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.