Department of Medical Microbiology and Radboud Centre of Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.
Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Front Immunol. 2022 Jul 18;13:930956. doi: 10.3389/fimmu.2022.930956. eCollection 2022.
Individuals infected with 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.
个体感染后会对红细胞内配子体蛋白和感染红细胞表面表达的外排配子体蛋白产生抗体反应。然而，目前对于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知之甚少。在这项研究中，我们通过 ELISA、多重珠基抗体分析和蛋白质微阵列评估了两项人体疟疾感染对照研究（CHMI）参与者的抗体反应。通过比较有和无配子体暴露的参与者的抗体反应，我们旨在区分由无性和有性阶段寄生虫引起的抗体反应。我们表明，在单次疟疾感染后，即使暴露于相对较低的配子体密度（高达约 1600 个配子体/mL），疟原虫初染的个体也会诱导出显著的抗有性阶段体液免疫反应。与感染后第 21 天即可检测到的针对已充分表征的无性血期抗原的抗体反应不同，对性期抗原（包括传播阻断疫苗候选物 Pfs48/45 和 Pfs230）的反应仅在感染后 51 天出现。我们发现以前与早期配子体或抗配子体免疫相关的抗原在与配子体暴露相关的反应中高度表达。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信息，并确定了仅在有配子体暴露的个体中引发抗体反应的新型抗原。我们的研究结果为疟疾传染性储存库的血清学监测提供了目标识别，并通过描述主要感染后主要疫苗抗原的抗体反应为疫苗开发提供了支持。
