Department of Internal Medicine and Immunobiology, Yale University of Medicine, New Haven, CT, USA.
Vaccine. 2011 Oct 19;29(45):8147-55. doi: 10.1016/j.vaccine.2011.08.027. Epub 2011 Aug 18.
Influenza vaccines are less effective in older people than younger people. This impaired ability to protect older people from influenza viral lung infection has important implications as older people suffer a higher morbidity and mortality from influenza viral lung infection than younger people. Therefore, the development of novel effective vaccines that induce protection from influenza viral infections in older people are urgently needed. We had previously shown that direct linking the TLR5 activator, flagellin, to viral peptides induces effective immunity to viral antigens in young mice and people, respectively. In this study, we tested the efficacy of this vaccine platform with the hemagglutinin peptide of the influenza A strain virus (vaccine denoted as STF2.HA1-2) in protecting aged mice from subsequent influenza viral lung infection. We found that a 3.0 μg dose of the vaccine was effective in reducing mortality and increasing clinical well-being during influenza viral lung infection in aged mice. However, this effect was inferior to the response induced in young mice. Defects in the adaptive immune system but not the innate immune system were associated with this reduced effectiveness of the vaccine with aging. Our results indicate that the STF2.HA1-2 vaccine is effective in protecting aged hosts from influenza lung infection, although defects in the adaptive immune system with aging may limit the effectiveness of this vaccine in older people.
流感疫苗在老年人中的效果不如在年轻人中。这种保护老年人免受流感病毒肺部感染的能力受损，对老年人因流感病毒肺部感染而导致的发病率和死亡率高于年轻人具有重要意义。因此，迫切需要开发新型有效的疫苗，以诱导老年人对流感病毒感染产生保护作用。我们之前曾表明，将 TLR5 激活剂鞭毛蛋白与病毒肽直接连接，分别诱导年轻小鼠和人群对病毒抗原产生有效的免疫。在这项研究中，我们用流感 A 株病毒的血凝素肽（疫苗表示为 STF2.HA1-2）来测试该疫苗平台在保护老年小鼠免受随后的流感病毒肺部感染中的功效。我们发现，3.0μg 剂量的疫苗可有效降低感染流感病毒的老年小鼠的死亡率并提高其临床健康状况。然而，这种效果不如在年轻小鼠中诱导的效果好。与这种疫苗效果降低相关的是适应性免疫系统的缺陷，而不是固有免疫系统的缺陷。我们的结果表明，STF2.HA1-2 疫苗可有效保护老年宿主免受流感肺部感染，但随着年龄的增长，适应性免疫系统的缺陷可能会限制这种疫苗在老年人中的效果。
