Nasal and systemic immune responses correlate with viral shedding after influenza challenge in people with complex preexisting immunity

IF 14.6 1区 医学 Q1 CELL BIOLOGY
Kathie-Anne Walters, Charles A. Blatti, Ruoqing Zhu, Barbara Banbury, Luca T. Giurgea, Rachel Bean, Eugene Han, Yuhan Li, Kelsey Scherler, Jenna Sherry, Sarah Formentini, Wenzhuo Zhou, Adriana Cervantes-Medina, Monica Gouzoulis, Luz Angela Rosas, Alison Han, Lisa Gatzke, Colleen Bushell, Ned Sherry, Jeffery K. Taubenberger, Matthew J. Memoli, John C. Kash
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Abstract

Each year in the United States, ~50% of adults ≥18 years old are vaccinated against influenza viruses, with protective efficacy averaging 40.5% over the past 20 years. To model annual seasonal influenza, a cohort of 74 adults, who were unscreened for preexisting A/H1N1 immunity and half of whom were recently immunized with licensed QIV (mean of 64 days), were challenged with A/H1N1 influenza virus. Transcriptomic, proteomic, and VDJ repertoire analyses were performed on nasal and peripheral blood samples from participants to identify nasal mucosal and systemic immune responses that correlated with viral shedding and immune correlates of protection. Viral-shedding participants showed increased T cell, but not B cell, VDJ diversity with expansion of low-frequency B cell clones postchallenge, including broadly neutralizing motifs. Nonshedding participants demonstrated decreased clonality and increased richness of B and T cell VDJ clones, increased preinoculation nasal mucosal immune gene and serum protein expression, and increased ex vivo peripheral blood mononuclear cell responses. Nasal mucosal responses in participants shedding virus for 2 or more days showed higher early viral loads and exhibited stronger induction of antiviral responses compared with those in participants who shed virus for 1 day. Last, participants with a single day of viral shedding were three times more likely to be female. These data shed light on the complex immune responses in the nasal mucosa and the periphery after influenza vaccination and infection, which will be critical for next-generation vaccine development.
鼻腔和全身免疫反应与流感攻击后病毒脱落相关的人有复杂的预先存在的免疫力
在美国,每年约有50%≥18岁的成年人接种流感病毒疫苗,过去20年的平均保护效果为40.5%。为了模拟年度季节性流感,74名成年人接受了a /H1N1流感病毒的挑战,这些成年人之前没有进行a /H1N1免疫筛查,其中一半最近接受了许可的QIV免疫(平均64天)。对参与者的鼻腔和外周血样本进行转录组学、蛋白质组学和VDJ全库分析,以确定与病毒脱落和免疫保护相关的鼻黏膜和全身免疫反应。病毒脱落的参与者表现出T细胞增加,但B细胞没有,VDJ多样性随着攻击后低频B细胞克隆的扩增而增加,包括广泛中和的基元。未脱落的参与者表现出B细胞和T细胞VDJ克隆的克隆性降低和丰富度增加,接种前鼻黏膜免疫基因和血清蛋白表达增加,体外外周血单个核细胞反应增加。与病毒脱落1天的受试者相比,脱落2天或更长时间的受试者鼻黏膜反应显示出更高的早期病毒载量,并表现出更强的抗病毒反应诱导。最后,有一天病毒脱落的参与者是女性的可能性是女性的三倍。这些数据揭示了流感疫苗接种和感染后鼻黏膜和外周的复杂免疫反应,这将对下一代疫苗的开发至关重要。
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来源期刊
Science Translational Medicine
Science Translational Medicine CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
26.70
自引率
1.20%
发文量
309
审稿时长
1.7 months
期刊介绍: Science Translational Medicine is an online journal that focuses on publishing research at the intersection of science, engineering, and medicine. The goal of the journal is to promote human health by providing a platform for researchers from various disciplines to communicate their latest advancements in biomedical, translational, and clinical research. The journal aims to address the slow translation of scientific knowledge into effective treatments and health measures. It publishes articles that fill the knowledge gaps between preclinical research and medical applications, with a focus on accelerating the translation of knowledge into new ways of preventing, diagnosing, and treating human diseases. The scope of Science Translational Medicine includes various areas such as cardiovascular disease, immunology/vaccines, metabolism/diabetes/obesity, neuroscience/neurology/psychiatry, cancer, infectious diseases, policy, behavior, bioengineering, chemical genomics/drug discovery, imaging, applied physical sciences, medical nanotechnology, drug delivery, biomarkers, gene therapy/regenerative medicine, toxicology and pharmacokinetics, data mining, cell culture, animal and human studies, medical informatics, and other interdisciplinary approaches to medicine. The target audience of the journal includes researchers and management in academia, government, and the biotechnology and pharmaceutical industries. It is also relevant to physician scientists, regulators, policy makers, investors, business developers, and funding agencies.
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