Aging is characterized by a progressive decline in the capacity of the immune system to fight influenza virus infection and to respond to vaccination. Among the several factors involved, in addition to increased frailty and high-risk conditions, the age-associated decrease in cellular and humoral immune responses plays a relevant role. This is in large part due to inflammaging, the chronic low-grade inflammatory status of the elderly, associated with intrinsic inflammation of the immune cells and decreased immune function. Aging is usually associated with reduced influenza virus-specific and influenza vaccine-specific antibody responses but some elderly individuals with higher pre-exposure antibody titers, due to a previous infection or vaccination, have less probability to get infected. Examples of this exception are the elderly individuals infected during the 2009 pandemic season who made antibodies with broader epitope recognition and higher avidity than those made by younger individuals. Several studies have allowed the identification of B cell intrinsic defects accounting for sub-optimal antibody responses of elderly individuals. These defects include 1) reduced class switch recombination, responsible for the generation of a secondary response of class switched antibodies, 2) reduced de novo somatic hypermutation of the antibody variable region, 3) reduced binding and neutralization capacity, as well as binding specificity, of the secreted antibodies, 4) increased epigenetic modifications that are associated with lower antibody responses, 5) increased frequencies of inflammatory B cell subsets, and 6) shorter telomeres. Although influenza vaccination represents the most effective way to prevent influenza infection, vaccines with greater immunogenicity are needed to improve the response of elderly individuals. Recent advances in technology have made possible a broad approach to better understand the age-associated changes in immune cells, needed to design tailored vaccines and effective therapeutic strategies that will be able to improve the immune response of vulnerable individuals.

中文翻译：

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衰老会导致 B 细胞缺陷并降低对流感感染和疫苗接种的抗体反应

衰老的特点是免疫系统对抗流感病毒感染和对疫苗接种作出反应的能力逐渐下降。在所涉及的几个因素中，除了虚弱和高风险状况的增加外，与年龄相关的细胞和体液免疫反应的降低也起着相关作用。这在很大程度上是由于炎症，老年人的慢性低度炎症状态，与免疫细胞的内在炎症和免疫功能下降有关。衰老通常与流感病毒特异性和流感疫苗特异性抗体反应降低有关，但由于先前感染或接种疫苗，一些具有较高暴露前抗体滴度的老年人被感染的可能性较小。这种例外的例子是在 2009 年大流行季节感染的老年人，他们产生的抗体比年轻人产生的抗体具有更广泛的表位识别和更高的亲和力。几项研究已经允许识别 B 细胞内在缺陷，解释老年人的次优抗体反应。这些缺陷包括 1) 减少的类别转换重组，负责产生类别转换抗体的二次反应，2) 减少抗体可变区的从头体细胞超突变，3) 降低的结合和中和能力，以及结合特异性，分泌的抗体，4) 增加与较低抗体反应相关的表观遗传修饰，5) 增加炎症 B 细胞亚群的频率，以及 6) 更短的端粒。虽然流感疫苗接种代表了预防流感感染的最有效方法，但需要具有更高免疫原性的疫苗来提高老年人的反应。最近的技术进步使我们有可能采用更广泛的方法来更好地了解免疫细胞中与年龄相关的变化，这需要设计量身定制的疫苗和有效的治疗策略，以改善脆弱个体的免疫反应。