ABSTRACT

Introduction:

The licensed seasonal influenza vaccines predominantly induce neutralizing antibodies against immunodominant hypervariable epitopes of viral surface proteins, with limited protection against antigenically distant influenza viruses. Strategies have been developed to improve vaccines’ performance in terms of broadly reactive and long-lasting immune response induction.

Areas covered:

We have summarized the advancements in the development of cross-protective influenza vaccines and discussed the challenges in evaluating them in preclinical and clinical trials. Here, the literature regarding the current stage of development of universal influenza vaccine candidates was reviewed

Expert opinion:

Although various strategies aim to redirect adaptive immune responses from variable immunodominant to immunosubdominant antigens, more conserved epitopes are being investigated. Approaches that improve antibody responses to conserved B cell epitopes have increased the protective efficacy of vaccines within a subtype or phylogenetic group of influenza viruses. Vaccines that elicit significant levels of T cells recognizing highly conserved viral epitopes possess a high cross-protective potential and may cover most circulating influenza viruses. However, the development of T cell-based universal influenza vaccines is challenging owing to the diversity of MHCs in the population, unpredictable degree of immunodominance, lack of adequate animal models, and difficulty in establishing T cell immunity in humans.

ABBREVIATIONS

cHA: chimeric HA; HBc: hepatitis B virus core protein; HA: hemagglutinin; HLA: human leucocyte antigen; IIV: inactivated influenza vaccine; KLH: keyhole limpet hemocyanin; LAH: long alpha helix; LAIV: live attenuated influenza vaccine; M2e: extracellular domain of matrix 2 protein; MHC: major histocompatibility complex; mRNA: messenger ribonucleic acid; NA: neuraminidase; NS1: non-structural protein 1; qNIV: quadrivalent nanoparticle influenza vaccine; T_RM: tissue-resident memory T cells; VE: vaccine effectiveness; VLP: virus-like particles; VSV: vesicular stomatitis virus

中文翻译：

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流感疫苗：引发广泛免疫反应的疫苗的进展

摘要

介绍：

获得许可的季节性流感疫苗主要诱导针对病毒表面蛋白的免疫显性高变表位的中和抗体，对抗原性遥远的流感病毒的保护有限。已经制定了策略来提高疫苗在广泛反应和持久免疫反应诱导方面的性能。

涵盖领域：

我们总结了交叉保护性流感疫苗开发的进展，并讨论了在临床前和临床试验中评估它们的挑战。本文回顾了有关通用流感疫苗候选开发当前阶段的文献

专家意见：

尽管各种策略旨在将适应性免疫反应从可变免疫显性抗原重定向到免疫亚显性抗原，但正在研究更保守的表位。改善对保守 B 细胞表位的抗体反应的方法提高了疫苗在流感病毒亚型或系统发育组中的保护效力。诱导显着水平的 T 细胞识别高度保守的病毒表位的疫苗具有很高的交叉保护潜力，可以覆盖大多数流行的流感病毒。然而，由于人群中 MHC 的多样性、不可预测的免疫优势程度、缺乏足够的动物模型以及难以在人体中建立 T 细胞免疫，开发基于 T 细胞的通用流感疫苗具有挑战性。

缩写

cHA：嵌合 HA；HBc：乙型肝炎病毒核心蛋白；HA：血凝素；HLA：人白细胞抗原；IIV：灭活流感疫苗；KLH：匙孔血蓝蛋白；LAH：长α螺旋；LAIV：流感减毒活疫苗；M2e：基质2蛋白的细胞外结构域；MHC：主要组织相容性复合体；mRNA：信使核糖核酸；NA：神经氨酸酶；NS1：非结构蛋白1；qNIV：四价纳米颗粒流感疫苗；T _RM：组织驻留记忆T细胞；VE：疫苗有效性；VLP：病毒样颗粒；VSV：水疱性口炎病毒