Unveiling an Immunological Mystery: Deciphering the Durability Divide in Vaccine-Elicited Antibody Responses.

IF 1 4区 医学 Q4 IMMUNOLOGY
George K Lewis, Stanca Ciupe, Mohammad Sajadi
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引用次数: 0

Abstract

Achieving durable antibody-mediated protection remains critical in vaccine develop-ment, particularly for viral diseases like COVID-19 and HIV. We discuss factors influencing an-tibody durability, highlighting the role of long-lived plasma cells (LLPCs) in the bone marrow, which are essential for sustained antibody production over many years. The frequencies and prop-erties of bone marrow LLPC are critical determinants of the broad spectrum of antibody durability for different vaccines. Vaccines for diseases like measles and mumps elicit long-lasting antibod-ies; those for COVID-19 and HIV do not. High epitope densities in the vaccine are known to favor antibody durability, but we discuss three underappreciated variables that also play a role in long-lived antibody responses. First, in addition to high epitope densities, we discuss the im-portance of CD21 as a critical determinant of antibody durability. CD21 is a B cell antigen recep-tor (BCR) complex component. It significantly affects BCR signaling strength in a way essential for generating LLPC in the bone marrow. Second, all antibody-secreting cells (ASC) are not cre-ated equal. There is a four-log range of antibody secretion rates, and we propose epigenetic im-printing of different rates on ASC, including LLPC, as a factor in antibody durability. Third, antibody durability afforded by bone marrow LLPC is independent of continuous antigenic stim-ulation. By contrast, tissue-resident T-bet+CD21low ASC also persists in secondary lymphoid tissues and continuously produces antibodies depending on persisting antigen and the tissue mi-croenvironment. We discuss these variables in the context of making an HIV vaccine that elicits broadly neutralizing antibodies against HIV that persist at protective levels without continuous vaccination over many years.

揭开免疫学之谜:解读疫苗引发的抗体反应的持久性差异。
实现持久的抗体介导保护仍然是疫苗开发的关键,特别是针对COVID-19和艾滋病毒等病毒性疾病。我们讨论了影响抗体耐久性的因素,强调了骨髓中长寿命浆细胞(llpc)的作用,它们对于多年来持续产生抗体至关重要。骨髓LLPC的频率和特性是不同疫苗的广谱抗体持久性的关键决定因素。麻疹和腮腺炎等疾病的疫苗会产生持久的抗体;COVID-19和艾滋病毒则不然。已知疫苗中的高表位密度有利于抗体耐久性,但我们讨论了三个未被重视的变量,它们也在长期抗体反应中发挥作用。首先,除了高表位密度外,我们还讨论了CD21作为抗体耐久性关键决定因素的重要性。CD21是一种B细胞抗原受体复合物。它显著影响BCR信号强度,这是在骨髓中产生LLPC所必需的。其次,并非所有的抗体分泌细胞(ASC)都是一样的。抗体分泌率有4个对数范围,我们提出在ASC(包括LLPC)上进行不同速率的表观遗传印迹,作为抗体持久性的一个因素。第三,骨髓LLPC提供的抗体耐久性不依赖于持续的抗原刺激。相比之下,组织常驻T-bet+CD21low ASC也持续存在于次级淋巴组织中,并依靠持续抗原和组织微环境不断产生抗体。我们在制作HIV疫苗的背景下讨论这些变量,这种疫苗可以引起广泛中和的抗HIV抗体,这些抗体在没有连续接种多年的情况下保持在保护水平。
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来源期刊
Current HIV Research
Current HIV Research 医学-病毒学
CiteScore
1.90
自引率
10.00%
发文量
81
审稿时长
6-12 weeks
期刊介绍: Current HIV Research covers all the latest and outstanding developments of HIV research by publishing original research, review articles and guest edited thematic issues. The novel pioneering work in the basic and clinical fields on all areas of HIV research covers: virus replication and gene expression, HIV assembly, virus-cell interaction, viral pathogenesis, epidemiology and transmission, anti-retroviral therapy and adherence, drug discovery, the latest developments in HIV/AIDS vaccines and animal models, mechanisms and interactions with AIDS related diseases, social and public health issues related to HIV disease, and prevention of viral infection. Periodically, the journal invites guest editors to devote an issue on a particular area of HIV research of great interest that increases our understanding of the virus and its complex interaction with the host.
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