Seminars in Immunology最新文献_第3页

Uncovered role of Th9 and IL-9 in rheumatoid arthritis: Current status and future directions Th9和IL-9在类风湿关节炎中的作用：现状和未来方向

IF 7.4 2区医学 Q1 IMMUNOLOGY

Seminars in Immunology

Pub Date : 2025-07-21 DOI: 10.1016/j.smim.2025.101979

Jiajie Tu , Weile Chen , Zimeng Xue , Lai-Shan Tam , Wei Wei

Early studies on T helper (Th) 9 cells and their specific cytokine IL-9 mainly focused on the field of allergic diseases. In addition to pathological studies, IL-9 can also affect the normal development and various functions of T cells and B cells. In recent years, a series of studies have found that IL-9 may play a pathogenic role in a range of autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and multiple sclerosis (MS). Specifically, Th9 cells and IL-9 show abnormally high expression in peripheral blood, synovial fluid, and synovial tissue of patients with RA. Based on this, therapeutic strategies targeting IL-9, such as monoclonal antibodies, have become potential treatments for RA. However, research on Th9 and IL-9 in RA has only been conducted for less than two decades, and many issues are worth further exploration. This article reviews the molecular mechanisms underlying the pathogenic effects of Th9 and IL-9 in RA, summarizes the potential reasons for inducing abnormally high expression of Th9 and IL-9 in RA, and discusses future research directions. The existing evidence shows that Th9-derived IL-9 is a potential biomarker or therapeutic target in RA. We hope that this current review can play a bridging role and provide new ideas for the study of Th9 and IL-9 in RA.

早期对辅助性T (Th) 9细胞及其特异性细胞因子IL-9的研究主要集中在过敏性疾病领域。除了病理研究外，IL-9还可以影响T细胞和B细胞的正常发育和各种功能。近年来，一系列研究发现IL-9可能在一系列自身免疫性疾病中发挥致病作用，包括类风湿关节炎（RA）、系统性红斑狼疮（SLE）、多发性硬化症（MS）等。具体来说，Th9细胞和IL-9在RA患者的外周血、滑液和滑液组织中异常高表达。基于此，针对IL-9的治疗策略，如单克隆抗体，已成为治疗RA的潜在方法。然而，关于Th9和IL-9在RA中的作用的研究才进行了不到二十年，还有很多问题值得进一步探索。本文综述了Th9和IL-9在RA中致病的分子机制，总结了在RA中诱导Th9和IL-9异常高表达的可能原因，并对未来的研究方向进行了探讨。现有证据表明，th9衍生的IL-9是RA的潜在生物标志物或治疗靶点。我们希望本综述能够起到桥梁作用，为RA中Th9和IL-9的研究提供新的思路。

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引用次数: 0

Discovery and characterization of vertebrate sialoglycan-binding proteins 脊椎动物唾液聚糖结合蛋白的发现与表征

IF 7.4 2区医学 Q1 IMMUNOLOGY

Seminars in Immunology

Pub Date : 2025-07-18 DOI: 10.1016/j.smim.2025.101978

Liran Adler , Sharon Yehuda , Ajit Varki , Vered Padler-Karavani

All known life forms feature a dense ensemble of cell surface and extracellular glycans. In vertebrates this includes a high density of sialic acids (Sias), a family of acidic sugars typically capping glycans of cell surface or secreted glycoproteins and glycolipids. Since Sia was found to be the receptor for the influenza virus, many other pathogens have since been shown to recognize specific host sialoglycans as targets for their hemagglutinins, adhesins and toxins, often with remarkable specificity and high affinity/avidity. Other pathogens have evolved diverse mechanisms to evade host immunity by ‘molecular mimicry’ of host sialoglycans. Sialic acids also act as “biological masks”, preventing access to underlying structures. Until the late 1970s, it was assumed that endogenous sialoglycan-binding proteins (SGBPs) did not exist in vertebrates. Several such vSGBPs have since been discovered, characterized by distinct sialoglycan specificities but generally low affinity. Markedly different rates of evolution and “Red Queen” effects likely explain this striking difference from the high specificity and affinity/avidity of numerous microbial SGBPs (mSGBPs). Nevertheless, these vSGBPs play important roles in normal development, physiology and disease conditions, with implications for human evolution. This review describes the discovery and characterization of vSGBPs. Most are previously known proteins, and their sialoglycan recognition had been discovered serendipitously. Thus, we may be seeing the ‘tip of an iceberg’ with many more such proteins to be discovered. We also emphasize recent studies showing that SGBP properties are markedly affected by competing endogenous Sialomes, such that in vitro studies may need to be re-visited, under conditions present in vivo.

所有已知的生命形式都具有细胞表面和细胞外聚糖的密集集合。在脊椎动物中，这包括高密度的唾液酸（Sias），这是一类酸性糖，通常覆盖在细胞表面的聚糖或分泌的糖蛋白和糖脂上。自从Sia被发现是流感病毒的受体以来，许多其他病原体已经被证明可以识别特定的宿主唾液聚糖作为其血凝素、粘附素和毒素的靶标，通常具有显著的特异性和高亲和力/亲和性。其他病原体已经进化出多种机制，通过宿主唾液聚糖的“分子模仿”来逃避宿主免疫。唾液酸还起着“生物面具”的作用，防止进入底层结构。直到20世纪70年代末，人们一直认为内源性唾液聚糖结合蛋白（SGBPs）在脊椎动物中不存在。已经发现了几个这样的vSGBPs，其特点是具有明显的唾液聚糖特异性，但通常亲和力较低。明显不同的进化速率和“红皇后”效应可能解释了许多微生物SGBPs （mSGBPs）的高特异性和亲和力/亲和性之间的显著差异。然而，这些vSGBPs在正常发育、生理和疾病状况中发挥重要作用，对人类进化具有影响。本文综述了vSGBPs的发现和特征。大多数是以前已知的蛋白质，它们的唾液聚糖识别是偶然发现的。因此，我们可能看到了“冰山一角”，还有更多这样的蛋白质有待发现。我们还强调，最近的研究表明，SGBP的特性明显受到内源性唾液体的影响，因此，在体内存在的条件下，体外研究可能需要重新进行。

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引用次数: 0

A framework for the rational design of oncolytic viruses: A holistic perspective considering the tumour microenvironment 溶瘤病毒合理设计的框架：考虑肿瘤微环境的整体视角

IF 7.4 2区医学 Q1 IMMUNOLOGY

Seminars in Immunology

Pub Date : 2025-06-25 DOI: 10.1016/j.smim.2025.101977

Dylan Thomas , Priya Bharadwa , Timothy Lee , Carolina S. Ilkow

Oncolytic viruses have played a pioneering role in establishing immunotherapies as the next generation of anti-cancer medicines. Recent works have highlighted the impact the tumour microenvironment has on the efficacy of immunotherapies like oncolytic viruses, as well as the ability of oncolytic viruses to modulate and reconfigure this microenvironment. Within this review, we examine the vast and increasing evidence highlighting the pivotal role of tumour microenvironment in dictating oncolytic virotherapy efficacy, while also discussing potential avenues for the future development of oncolytic viruses. Following introductions to commonly used oncolytic viruses and components of the tumour microenvironment, we highlight recent research investigating their reciprocal relationships. Finally, innovations in 3D modelling to reconstitute the tumour microenvironment ex vivo are discussed, followed by examination of successful case studies in which tumour microenvironment dynamics have informed the rational design of successful and tailored oncolytic viruses. Through this, we provide evidence that substantial tumour heterogeneity amongst patients and tumour types significantly impedes effective oncolytic virotherapy, thus we suggest that consideration of each unique tumour microenvironment’s dynamics is critical for the design of functional and efficacious oncolytic virotherapy – both as a monotherapy or in combination with other cancer therapies.

溶瘤病毒在建立免疫疗法作为下一代抗癌药物方面发挥了开创性的作用。最近的研究强调了肿瘤微环境对溶瘤病毒等免疫疗法疗效的影响，以及溶瘤病毒调节和重新配置这种微环境的能力。在这篇综述中，我们研究了大量和越来越多的证据，强调肿瘤微环境在决定溶瘤病毒治疗效果中的关键作用，同时也讨论了溶瘤病毒未来发展的潜在途径。在介绍了常用的溶瘤病毒和肿瘤微环境的组成部分之后，我们重点介绍了研究它们相互关系的最新研究。最后，讨论了三维建模的创新，以重建体外肿瘤微环境，随后检查了成功的案例研究，其中肿瘤微环境动力学为成功和量身定制的溶瘤病毒的合理设计提供了信息。通过这项研究，我们提供的证据表明，患者和肿瘤类型之间的肿瘤异质性显著阻碍了有效的溶瘤病毒治疗，因此我们建议考虑每个独特的肿瘤微环境动力学对于设计功能性和有效的溶瘤病毒治疗至关重要-无论是作为单一治疗还是与其他癌症治疗联合使用。

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引用次数: 0

Local and Cell-intrinsic complement: The new player in cancer progression 局部和细胞内在补体：癌症进展的新参与者

IF 7.4 2区医学 Q1 IMMUNOLOGY

Seminars in Immunology

Pub Date : 2025-06-24 DOI: 10.1016/j.smim.2025.101976

M. Revel , N.S. Merle

The complement system, a key component of innate immunity, has a paradoxical role in cancer, acting both as a tumor suppressor and a promoter. While traditionally recognized for its extracellular immune functions, recent discoveries highlight non-canonical, intracellular roles in tumor progression. These findings challenge the conventional view that complement activity is confined to the extracellular space and reveal its unexpected influence on tumor proliferation, immune evasion, and metastasis. Tumors exploit local complement activation to create an immunosuppressive microenvironment, often upregulating regulatory proteins to evade complement-mediated cytotoxicity. Complement proteins can also promote tumor growth and therapy resistance through extracellular signaling and intracellular interactions with oncogenic pathways. The emerging concept of an intracellular complement system, or "complosome," further suggests roles in cell metabolism, immune modulation, and stress responses. Despite these insights, key challenges remain in defining cell-specific complement functions and distinguishing autocrine, paracrine, and intracellular signaling. Current studies rely heavily on gene expression data, which do not fully reflect protein activity. Advances in gene editing, single-cell technologies, and intracellular complement inhibitors will be critical for clarifying the complex roles of complement in cancer and identifying new therapeutic strategies.

作为先天免疫的关键组成部分，补体系统在癌症中扮演着一个矛盾的角色，既是肿瘤抑制因子，又是肿瘤启动因子。虽然传统上认为它是细胞外免疫功能，但最近的发现强调了肿瘤进展中非典型的细胞内作用。这些发现挑战了补体活性局限于细胞外空间的传统观点，并揭示了其对肿瘤增殖、免疫逃避和转移的意想不到的影响。肿瘤利用局部补体激活创造免疫抑制微环境，经常上调调节蛋白以逃避补体介导的细胞毒性。补体蛋白还可以通过细胞外信号传导和细胞内与致癌途径的相互作用促进肿瘤生长和治疗抵抗。细胞内补体系统或“复合体”的新概念进一步表明，它在细胞代谢、免疫调节和应激反应中的作用。尽管有这些见解，关键的挑战仍然存在于定义细胞特异性补体功能和区分自分泌、旁分泌和细胞内信号。目前的研究严重依赖于基因表达数据，这并不能完全反映蛋白质的活性。基因编辑、单细胞技术和细胞内补体抑制剂的进展对于阐明补体在癌症中的复杂作用和确定新的治疗策略至关重要。

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引用次数: 0

Oncolytic virus-mediated immunomodulation in glioblastoma: Insights from clinical trials and challenges 胶质母细胞瘤中溶瘤病毒介导的免疫调节：来自临床试验和挑战的见解

IF 7.4 2区医学 Q1 IMMUNOLOGY

Seminars in Immunology

Pub Date : 2025-06-23 DOI: 10.1016/j.smim.2025.101975

Raziye Piranlioglu , E. Antonio Chiocca

The pivotal involvement of the host immune system in cancer therapy has dramatically reshaped therapeutic paradigms, inaugurating the era of immunotherapy. Nonetheless, antigen-specific immunotherapies encounter substantial hurdles within the highly immunosuppressive microenvironment of glioblastoma (GBM), which thwarts antitumor T-cell immunity. Oncolytic viruses (OVs), a form of immunotherapy that inflames the GBM microenvironment, have been subject to clinical evaluation, yielding promising outcomes. Evidence increasingly indicates that OVs can modify the GBM microenvironment from an immunosuppressive to an immune active state, facilitating enhanced antitumor responses. Clinical trials demonstrate that oncolytic virotherapy is generally well-tolerated, generating data about its immune-activating effects. "Window of opportunity" trials provide insights into viral replication, pre-existing immunity, and delivery methods. However, constraints in post-treatment sampling may impede comprehensive analyses of the virotherapy-induced biological and immunological changes. This review discusses current advancements and persistent challenges in GBM trials involving OVs.

宿主免疫系统在癌症治疗中的关键作用极大地重塑了治疗范式，开创了免疫治疗的时代。尽管如此，抗原特异性免疫疗法在胶质母细胞瘤（GBM）的高度免疫抑制微环境中遇到了实质性障碍，这阻碍了抗肿瘤t细胞免疫。溶瘤病毒（OVs）是一种使GBM微环境发炎的免疫疗法，已经进行了临床评估，产生了有希望的结果。越来越多的证据表明，OVs可以将GBM微环境从免疫抑制状态改变为免疫活性状态，促进抗肿瘤反应的增强。临床试验表明，溶瘤病毒治疗通常耐受良好，产生了有关其免疫激活作用的数据。“机会之窗”试验提供了对病毒复制、预先免疫和递送方法的深入了解。然而，治疗后采样的限制可能会阻碍对病毒治疗诱导的生物学和免疫学变化的全面分析。本综述讨论了涉及OVs的GBM试验的当前进展和持续挑战。

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引用次数: 0

An evolutionary perspective of the roles of galectins in pathogen recognition and immunity 凝集素在病原体识别和免疫中的作用的进化观点

IF 7.4 2区医学 Q1 IMMUNOLOGY

Seminars in Immunology

Pub Date : 2025-06-16 DOI: 10.1016/j.smim.2025.101974

Gerardo R. Vasta , Gabriel A. Rabinovich

Protein-glycan interactions, mediated by lectins, are essential for diverse physiological processes, including glycoprotein processing, cell adhesion, communication, signaling, and immune recognition. Lectins, classified into families like C-type, I-type, F-type, and galectins, recognize specific glycans on macromolecules through their carbohydrate recognition domains (CRDs). Galectins, characterized by their β-galactoside binding and conserved CRD structure, exhibit remarkable functional diversification across evolution. Initially associated with developmental roles, they are now implicated in cancer, angiogenesis, and immune homeostasis. Furthermore, they interact with glycans on both beneficial and pathogenic microorganisms. While host galectins facilitate mutualistic interactions, pathogens can exploit this recognition for infection and manipulate host glycosylation to subvert galectin functions. The ability of galectins to recognize both self and non-self glycans, evident even in early metazoans, underscores their evolutionary versatility and raises questions about their primordial function and their evolutionary trajectory. This review explores the evolving roles of galectins, highlighting their adaptability and the complex interplay between host and pathogen interactions.

凝集素介导的蛋白-聚糖相互作用对多种生理过程至关重要，包括糖蛋白加工、细胞粘附、通讯、信号传导和免疫识别。凝集素可分为c型、i型、f型和凝集素，它们通过碳水化合物识别结构域（CRDs）识别大分子上的特定聚糖。半乳糖凝集素以其β-半乳糖苷结合和保守的CRD结构为特征，在进化过程中表现出显著的功能多样化。它们最初与发育有关，现在与癌症、血管生成和免疫稳态有关。此外，它们在有益和致病微生物上与聚糖相互作用。当宿主凝集素促进相互作用时，病原体可以利用这种识别来感染并操纵宿主糖基化来破坏凝集素的功能。凝集素识别自我和非自我聚糖的能力，即使在早期后生动物中也很明显，强调了它们的进化多功能性，并提出了关于它们的原始功能和进化轨迹的问题。这篇综述探讨了凝集素的进化作用，强调了它们的适应性和宿主与病原体相互作用之间的复杂相互作用。

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引用次数: 0

The glycoimmune landscape in health and disease 健康和疾病中的糖免疫景观

IF 7.4 2区医学 Q1 IMMUNOLOGY

Seminars in Immunology

Pub Date : 2025-05-20 DOI: 10.1016/j.smim.2025.101965

Salomé S. Pinho , Gabriel A. Rabinovich

Emerging observations at the molecular, cellular, and organismal levels have unveiled critical roles for glycans in regulating a broad range of innate and adaptive immune cell processes. Through interactions with various families of glycan-binding proteins, including galectins, C-type lectins, and siglecs, glycans shape the nature, the fate and the function of immune cell types, modulating processes such as immune cell development, activation, differentiation, trafficking, exhaustion, and survival. Furthermore, dysregulated glycosylation pathways and altered glycan-binding receptor functions are associated with several pathological conditions, including infection, autoimmunity, and cancer. This special issue highlights the most recent updates and current challenges on the multifunctional roles of glycans and glycan-binding proteins in orchestrating, amplifying, or inhibiting immune responses. This collection seeks to enhance awareness of the significance of glycans in immunobiology and immunopathology from cellular, molecular, and evolutionary perspectives into clinical applications, underscoring their relevance as promising biomarkers and targets for designing novel immunotherapeutic approaches.

在分子、细胞和有机体水平上的新观察揭示了聚糖在调节广泛的先天和适应性免疫细胞过程中的关键作用。通过与各种聚糖结合蛋白家族（包括凝集素、c型凝集素和siglecs）的相互作用，聚糖塑造了免疫细胞类型的性质、命运和功能，调节了免疫细胞的发育、激活、分化、运输、衰竭和生存等过程。此外，糖基化途径失调和聚糖结合受体功能改变与多种病理状况有关，包括感染、自身免疫和癌症。本期特刊重点介绍了聚糖和聚糖结合蛋白在协调、放大或抑制免疫反应中的多功能作用的最新进展和当前的挑战。本收集旨在从细胞、分子和进化的角度提高对聚糖在免疫生物学和免疫病理学中的重要性的认识，并将其应用于临床应用，强调它们作为有前途的生物标志物和设计新型免疫治疗方法的靶点的相关性。

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引用次数: 0

Harnessing complement biomarkers for precision cancer care 利用补体生物标志物进行精准癌症治疗

IF 7.4 2区医学 Q1 IMMUNOLOGY

Seminars in Immunology

Pub Date : 2025-05-15 DOI: 10.1016/j.smim.2025.101963

Houcine Hamidi , Idris Boudhabhay , Marie-Agnes Dragon-Durey

The tumor microenvironment (TME) consists of various immune and non-immune cells, along with proteins from different origins, and plays a crucial role in tumor development, treatment response, and patient prognosis. Complement system is a key player in the TME. It is a proteolytic cascade that generates cleavage fragments capable to activate cells through specific receptors or deposit on cells and tissues. This review summarizes current data on the complement system as a potential biomarker in cancer. Transcriptomic analyses have classified tumors based on the impact of complement gene expression on prognosis. Immunostaining provides insights into the expression and deposition of complement proteins and fragments in tumors and TME cells. In body fluids such as blood, measuring complement activation fragments and detecting anti-complement autoantibodies have identified non-invasive biomarkers relevant to certain cancer types. With the rise of complement-targeting therapies and new tools for analyzing the complement system in tumors and body fluids, it is time to define its role in cancer management. This includes its potential for cancer detection, staging, and potentially for treatment monitoring.

肿瘤微环境（tumor microenvironment， TME）由多种免疫和非免疫细胞以及来自不同来源的蛋白质组成，在肿瘤的发展、治疗反应和患者预后中起着至关重要的作用。补体系统在TME中起着关键作用。它是一种蛋白水解级联反应，产生的裂解片段能够通过特定受体激活细胞或沉积在细胞和组织上。本文综述了补体系统作为癌症潜在生物标志物的最新研究数据。转录组学分析已经根据补体基因表达对预后的影响对肿瘤进行了分类。免疫染色提供了对肿瘤和TME细胞中补体蛋白和片段的表达和沉积的见解。在血液等体液中，测量补体激活片段和检测抗补体自身抗体已经确定了与某些癌症类型相关的非侵入性生物标志物。随着补体靶向治疗的兴起以及分析肿瘤和体液中补体系统的新工具的出现，是时候确定其在癌症治疗中的作用了。这包括它在癌症检测、分期和治疗监测方面的潜力。

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引用次数: 0

Unraveling the pathophysiology of narcolepsy type 1 through hypothesis-driven and hypothesis-generating approaches 通过假设驱动和假设生成方法揭示1型发作性睡病的病理生理学

IF 7.4 2区医学 Q1 IMMUNOLOGY

Seminars in Immunology

Pub Date : 2025-05-14 DOI: 10.1016/j.smim.2025.101962

Sean A. Freeman , Ikram Ayoub , Yves Dauvilliers , Roland S. Liblau

Narcolepsy type 1 (NT1) is a chronic orphan neurological sleep disorder characterized by the loss of hypocretin-producing neurons in the lateral hypothalamus, which play a crucial role in wakefulness. Given the genetic association with the HLA-DQB1 * 06:02 allele and environmental links with the 2009 influenza pandemic, many lines of evidence point towards an immune mechanism, notably autoimmunity, underlying the disease pathophysiology. Autoreactive T cells are found in the blood of NT1 patients, and mouse models demonstrate their migratory capacity and contribution in the selective destruction of hypocretin-producing neurons. However, direct evidence for their role in human NT1 pathophysiology remains elusive. In complementing these findings, hypothesis-generating approaches—including multiparametric immune profiling, transcriptomic sequencing and large-scale proteomic of blood and cerebrospinal fluid—have uncovered promising new avenues into the immune system’s involvement in NT1. In this review, we explore the mechanisms driving NT1 pathogenesis, emphasizing both hypothesis-driven and hypothesis-generating approaches, and discuss potential future directions that could pave the way for targeted immunotherapies.

1型发作性睡病（NT1）是一种慢性孤儿神经性睡眠障碍，其特征是下丘脑外侧分泌下丘脑激素的神经元的缺失，而下丘脑外侧分泌下丘脑激素的神经元在清醒中起着至关重要的作用。鉴于与HLA-DQB1 * 06:02等位基因的遗传关联以及与2009年流感大流行的环境联系，许多证据都指向一种免疫机制，特别是自身免疫，是疾病病理生理学的基础。在NT1患者的血液中发现了自身反应性T细胞，小鼠模型证明了它们的迁移能力和选择性破坏下丘脑分泌素神经元的作用。然而，它们在人类NT1病理生理中的作用的直接证据仍然难以捉摸。为了补充这些发现，假设生成方法-包括多参数免疫谱，转录组测序和血液和脑脊液的大规模蛋白质组学-为免疫系统参与NT1发现了有希望的新途径。在这篇综述中，我们探讨了驱动NT1发病机制的机制，强调了假设驱动和假设产生的方法，并讨论了可能为靶向免疫治疗铺平道路的潜在未来方向。

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引用次数: 0

Individual- and population-associated heterogeneity in vaccine-induced immune responses. The impact of inflammatory status and diabetic comorbidity 疫苗诱导免疫反应的个体和群体相关异质性。炎症状态和糖尿病合并症的影响

IF 7.4 2区医学 Q1 IMMUNOLOGY

Seminars in Immunology

Pub Date : 2025-05-09 DOI: 10.1016/j.smim.2025.101964

Simone A. Joosten

Vaccines induce quantitively and qualitatively different effector responses between populations but also between individuals within populations. Several factors are known to affect the success of vaccination, including age, gender, co-infections (e.g. HIV), pre-existing inflammatory status and co-morbidities such as type 2 diabetes mellitus (T2DM). These factors, either alone or in combination, strongly influence vaccine induced immunity and thereby possibly vaccine efficacy. Vaccination strategies should therefore not only be evaluated in young, healthy selected individuals but also in individuals with immune ageing, persisting inflammation and co-morbidities, and include the measurement of qualitative rather than only quantitative measures of vaccine effects.

疫苗在种群之间以及种群内个体之间诱导的效应反应在数量和质量上都存在差异。已知有几个因素会影响疫苗接种的成功，包括年龄、性别、合并感染（如艾滋病毒）、先前存在的炎症状况和合并疾病，如2型糖尿病（T2DM）。这些因素，无论是单独的还是联合的，都强烈影响疫苗诱导的免疫，从而可能影响疫苗的效力。因此，疫苗接种策略不仅应在选定的年轻健康个体中进行评估，而且也应在具有免疫老化、持续炎症和共病的个体中进行评估，并包括对疫苗效果的定性测量，而不仅仅是定量测量。

引用次数: 0