The acquisition of humoral immune responses targeting Plasmodium falciparum sexual stages in controlled human malaria infections.
The acquisition of humoral immune responses targeting Plasmodium falciparum sexual stages in controlled human malaria infections.
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DOI：
10.3389/fimmu.2022.930956
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发表时间：
2022
影响因子：
7.3
通讯作者：
Stone, Will J. R.
中科院分区：
文献类型：
--
作者：
de Jong, Roos M.;Alkema, Manon;Oulton, Tate;Dumont, Elin;Teelen, Karina;Nakajima, Rie;de Assis, Rafael Ramiro;Press, Kathleen W. Dantzler;Ngotho, Priscilla;Tetteh, Kevin K. A.;Felgner, Phil;Marti, Matthias;Collins, Katharine A.;Drakeley, Chris;Bousema, Teun;Stone, Will J. R.
关键词：
感染恶性疟原虫的个体会对红细胞内配子体蛋白产生抗体反应，并输出存在于受感染红细胞表面的配子体蛋白。然而，目前对配子体抗原的免疫原性和配子体诱导的抗体反应的特异性的了解有限。在这项研究中，我们通过 ELISA、基于微珠的多重抗体测定和蛋白质微阵列评估了两项对照人类疟疾感染 (CHMI) 研究参与者的抗体反应。通过比较有和没有配子体暴露的参与者的抗体反应，我们的目的是解开无性阶段和有性阶段寄生虫诱导的抗体反应。我们发现，在单次疟疾感染后，即使在暴露于相对较低的配子体密度（高达约 1,600 个配子体/mL）后，未接触过疟疾的个体也会诱发显着的抗性阶段体液反应。与感染后 21 天即可检测到的对已明确表征的无性血液阶段抗原的抗体反应相比，对有性阶段抗原（包括传播阻断疫苗候选 Pfs48/45 和 Pfs230）的反应仅在感染后 51 天才明显。我们发现以前与早期配子体或抗配子免疫相关的抗原在与配子体暴露相关的反应中高度代表。我们的数据提供了关于配子体抗体反应的诱导和动力学的详细见解，并鉴定了仅在接触配子体的个体中引发抗体反应的新抗原。我们的研究结果为监测疟疾传染源的血清学测定提供了目标鉴定，并通过描述初次感染后对主要疫苗抗原的抗体反应来支持疫苗开发。
Individuals infected with P. falciparum develop antibody responses to intra-erythrocytic gametocyte proteins and exported gametocyte proteins present on the surface of infected erythrocytes. However, there is currently limited knowledge on the immunogenicity of gametocyte antigens and the specificity of gametocyte-induced antibody responses. In this study, we assessed antibody responses in participants of two controlled human malaria infection (CHMI) studies by ELISA, multiplexed bead-based antibody assays and protein microarray. By comparing antibody responses in participants with and without gametocyte exposure, we aimed to disentangle the antibody response induced by asexual and sexual stage parasites. We showed that after a single malaria infection, a significant anti-sexual stage humoral response is induced in malaria-naïve individuals, even after exposure to relatively low gametocyte densities (up to ~1,600 gametocytes/mL). In contrast to antibody responses to well-characterised asexual blood stage antigens that were detectable by day 21 after infection, responses to sexual stage antigens (including transmission blocking vaccine candidates Pfs48/45 and Pfs230) were only apparent at 51 days after infection. We found antigens previously associated with early gametocyte or anti-gamete immunity were highly represented among responses linked with gametocyte exposure. Our data provide detailed insights on the induction and kinetics of antibody responses to gametocytes and identify novel antigens that elicit antibody responses exclusively in individuals with gametocyte exposure. Our findings provide target identification for serological assays for surveillance of the malaria infectious reservoir, and support vaccine development by describing the antibody response to leading vaccine antigens after primary infection.
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DOI：
10.1016/s1473-3099(21)00072-4
发表时间：
2021-11
期刊：
The Lancet. Infectious diseases
影响因子：
--
作者：
Andolina C;Rek JC;Briggs J;Okoth J;Musiime A;Ramjith J;Teyssier N;Conrad M;Nankabirwa JI;Lanke K;Rodriguez-Barraquer I;Meerstein-Kessel L;Arinaitwe E;Olwoch P;Rosenthal PJ;Kamya MR;Dorsey G;Greenhouse B;Drakeley C;Staedke SG;Bousema T
通讯作者：
Bousema T
影响因子：
17.1
作者：
Joice R;Nilsson SK;Montgomery J;Dankwa S;Egan E;Morahan B;Seydel KB;Bertuccini L;Alano P;Williamson KC;Duraisingh MT;Taylor TE;Milner DA;Marti M
通讯作者：
Marti M
影响因子：
1.5
作者：
ARDESHIR, F;HOWARD, RF;REESE, RT
通讯作者：
REESE, RT
DOI：
10.1073/pnas.1220360110
发表时间：
2013-05-07
影响因子：
11.1
作者：
Bijker, Else M.;Bastiaens, Guido J. H.;Sauerwein, Robert W.
通讯作者：
Sauerwein, Robert W.
影响因子：
16.6
作者：
Gruering, Christof;Heiber, Arlett;Spielmann, Tobias
通讯作者：
Spielmann, Tobias