Heterogeneity of the human immune response to malaria infection and vaccination driven by latent cytomegalovirus infection.

IF 9.7 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Reena Mukhiya, Wim A Fleischmann, Jessica R Loughland, Jo-Anne Chan, Fabian de Labastida Rivera, Dean Andrew, James G Beeson, James S McCarthy, Bridget E Barber, J Alejandro Lopez, Christian Engwerda, Richard Thomson-Luque, Michelle J Boyle
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引用次数: 0

Abstract

Background: Human immune responses to infection and vaccination are heterogenous, driven by multiple factors including genetics, environmental exposures and personal infection histories. For malaria caused by Plasmodium falciparum parasites, host factors that impact on humoral immunity are poorly understood.

Methods: We investigated the role of latent cytomegalovirus (CMV) on the host immune response to malaria using samples obtained from individuals in previously conducted Phase 1 trials of blood stage P. falciparum Controlled Human Malaria Infection (CHMI) and in a MSP1 vaccine clinical trial. Induced antibody and functions of antibodies, as well as CD4 T cell responses were quantified.

Findings: CMV seropositivity was associated with reduced induction of parasite specific antibodies following malaria infection and vaccination. During infection, reduced antibody induction was associated with modifications to the T -follicular helper (Tfh) cell compartment. CMV seropositivity was associated with a skew towards Tfh1 cell subsets before and after malaria infection, and reduced activation of Tfh2 cells. Protective Tfh2 cell activation was only associated with antibody development in individuals who were CMV seronegative, and a higher proportion of Tfh1 cells was associated with lower antibody development in individuals who were CMV seropositive. During MSP1 vaccination, reduced antibody induction in individuals who were CMV seropositive was associated with CD4 T cell expression of terminal differentiation marker CD57.

Interpretation: These findings suggest that CMV seropositivity may be negatively associated with malaria antibody development. Further studies in larger cohorts, particularly in malaria endemic regions are required to investigate whether CMV infection may modify immunity to malaria gained during infection or vaccination in children.

Funding: Work was funded by National Health and Medical Research Council of Australia, CSL Australia and Snow Medical Foundation. Funders had no role in data generation, writing of manuscript of decision to submit for publication.

潜伏巨细胞病毒感染驱动的人类对疟疾感染和疫苗接种的免疫反应的异质性。
背景:人类对感染和疫苗接种的免疫反应是多种多样的,受遗传、环境暴露和个人感染史等多种因素的影响。对于恶性疟原虫引起的疟疾,人们对影响体液免疫的宿主因素知之甚少:方法:我们利用之前进行的恶性疟原虫控制性人类疟疾感染(CHMI)一期试验和 MSP1 疫苗临床试验中获得的样本,研究了潜伏巨细胞病毒(CMV)对宿主疟疾免疫反应的作用。对诱导抗体、抗体功能以及 CD4 T 细胞反应进行了量化:研究结果:CMV 血清阳性与疟疾感染和接种疫苗后寄生虫特异性抗体诱导减少有关。在感染期间,抗体诱导的减少与T-滤泡辅助细胞(Tfh)区系的改变有关。在疟疾感染前后,CMV 血清阳性与 Tfh1 细胞亚群的倾斜以及 Tfh2 细胞的活化减少有关。保护性 Tfh2 细胞活化只与 CMV 血清阴性个体的抗体发展有关,而 Tfh1 细胞比例较高与 CMV 血清阳性个体的抗体发展较低有关。在接种 MSP1 疫苗期间,CMV 血清阳性者抗体诱导率的降低与 CD4 T 细胞表达末端分化标记物 CD57 有关:这些研究结果表明,CMV 血清阳性可能与疟疾抗体的形成呈负相关。需要在更大的群体中开展进一步研究,特别是在疟疾流行地区,以调查CMV感染是否会改变儿童在感染或接种疫苗期间获得的疟疾免疫力:工作由澳大利亚国家健康与医学研究委员会、澳大利亚CSL公司和斯诺医学基金会资助。资助方未参与数据生成、手稿撰写和决定是否提交发表。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
EBioMedicine
EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
17.70
自引率
0.90%
发文量
579
审稿时长
5 weeks
期刊介绍: eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.
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