OBJECTIVES Enhanced inactivated influenza vaccines (eIIV) aim to increase immunogenicity and protection compared with the widely used standard IIV (S-IIV). METHODS We tested four vaccines in parallel, FluZone high dose, FluBlok and FluAd versus S-IIV in a randomised controlled trial of older adults and in a mouse infection model to assess immunogenicity, protection from lethal challenge and mechanisms of action. RESULTS In older adults, FluAd vaccination stimulated a superior antibody profile, including H3-HA antibodies that were elevated for up to 1 year after vaccination, higher avidity H3HA IgG and larger HA stem IgG responses. In a mouse model, FluAd also elicited an earlier and larger induction of HA stem antibodies with increased germinal centre responses and upregulation and long-term expression of B-cell switch transcription factors. Long-term cross-reactive memory responses were sustained by FluAd following lethal heterosubtypic influenza challenge, with reduced lung damage and viral loads, coinciding with increased T- and B-cell recall. Advantages were also noted for the high-dose FluZone vaccine in both humans and mice. CONCLUSION The early, broadly reactive and long-lived antibody response of FluAd indicates a potential advantage of this vaccine, particularly in years when there is a mismatch between the vaccine strain and the circulating strain of influenza viruses.

中文翻译：

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对增强型流感疫苗接种的评估发现，FluAd 在小鼠和老年人中具有优势。

目的 与广泛使用的标准 IIV (S-IIV) 相比，增强型灭活流感疫苗 (eIIV) 旨在提高免疫原性和保护性。方法 我们在一项针对老年人的随机对照试验和小鼠感染模型中平行测试了四种疫苗，FluZone 高剂量、FluBlok 和 FluAd 与 S-IIV，以评估免疫原性、对致命攻击的保护和作用机制。结果 在老年人中，FluAd 疫苗接种刺激了更好的抗体谱，包括接种后长达 1 年的 H3-HA 抗体升高、更高的 H3HA IgG 亲和力和更大的 HA 茎 IgG 反应。在小鼠模型中，FluAd 还引发了更早和更大的 HA 干抗体诱导，增加了生发中心反应和 B 细胞转换转录因子的上调和长期表达。在致命的异亚型流感攻击后，FluAd 维持了长期的交叉反应记忆反应，肺损伤和病毒载量减少，同时 T 细胞和 B 细胞回忆增加。高剂量 FluZone 疫苗在人类和小鼠中也有优势。结论 FluAd 的早期、广泛反应和长寿命的抗体反应表明这种疫苗的潜在优势，特别是在疫苗株与流感病毒循环株之间存在不匹配的年份。