Irene N. Nkumama, Rodney Ogwang, Dennis Odera, Fauzia Musasia, Kennedy Mwai, Lydia Nyamako, Linda Murungi, James Tuju, Kristin Fürle, Micha Rosenkranz, Rinter Kimathi, Patricia Njuguna, Mainga Hamaluba, Melissa C. Kapulu, Roland Frank, , Faith H.A. Osier
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引用次数: 0
摘要
疟疾是一种威胁生命的疾病,对全球健康具有重要意义,尤其是在撒哈拉以南非洲地区。生长抑素测定 (GIA) 通常用于评估、优先考虑和量化疟疾血期候选疫苗的功效,但不能可靠地预测自然获得或疫苗诱导的保护。在半免疫志愿者中进行的受控人类疟疾挑战研究提供了一个无与伦比的机会,可以有力地确定保护的机理相关因素。我们利用这一平台,对与恶性疟原虫红细胞裂殖阶段免疫相关的七种功能抗体检测进行了正面比较。Fc 介导的效应功能与疟疾临床症状和寄生虫指数繁殖的保护密切相关,而金标准 GIA 则不然。Fc 介导的效应物功能的广度可区分挑战后的临床免疫力。这些发现改变了人们对疟疾免疫机制的认识,对疫苗开发具有重要意义。
Breadth of Fc-mediated effector function correlates with clinical immunity following human malaria challenge
Malaria is a life-threatening disease of global health importance, particularly in sub-Saharan Africa. The growth inhibition assay (GIA) is routinely used to evaluate, prioritize, and quantify the efficacy of malaria blood-stage vaccine candidates but does not reliably predict either naturally acquired or vaccine-induced protection. Controlled human malaria challenge studies in semi-immune volunteers provide an unparalleled opportunity to robustly identify mechanistic correlates of protection. We leveraged this platform to undertake a head-to-head comparison of seven functional antibody assays that are relevant to immunity against the erythrocytic merozoite stage of Plasmodium falciparum. Fc-mediated effector functions were strongly associated with protection from clinical symptoms of malaria and exponential parasite multiplication, while the gold standard GIA was not. The breadth of Fc-mediated effector function discriminated clinical immunity following the challenge. These findings present a shift in the understanding of the mechanisms that underpin immunity to malaria and have important implications for vaccine development.
期刊介绍:
Immunity is a publication that focuses on publishing significant advancements in research related to immunology. We encourage the submission of studies that offer groundbreaking immunological discoveries, whether at the molecular, cellular, or whole organism level. Topics of interest encompass a wide range, such as cancer, infectious diseases, neuroimmunology, autoimmune diseases, allergies, mucosal immunity, metabolic diseases, and homeostasis.