Vaccination is the most effective strategy to combat influenza. Ideally, potent and persistent vaccine effects would be induced with a single vaccine dose. Here, we designed a virus-like particle (VLP)-based vaccine presenting multiple copies of the influenza hemagglutinin (HA) from A/Puerto Rico/8/1934 (PR8HA-VLP) and examined its immunogenicity and protective efficacy in ferrets. Serum-neutralizing antibodies were effectively induced against the homologous virus at 3-week post-vaccination with a single dose of PR8HA-VLP with or without adjuvants. When the single-immunized ferrets were challenged with the homologous virus, virus replication in the nasal mucosa was significantly reduced. Long-term monitoring of serum titers revealed that after adjuvanted vaccination with PR8HA-VLP, neutralizing antibodies were retained at similar levels 20- to 183-week post-vaccination, although a 4- to 8-fold titer decline was observed from 3- to 20-week post-vaccination. Boost immunization at 183 weeks after the first immunization elicited higher neutralizing antibody titers than those at 3 weeks after the initial immunization in most of the animals. These results confirm that nanoparticle-based vaccines are a promising approach to effectively elicit durable multiyear neutralizing antibody responses against influenza viruses.

中文翻译：

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使用基于流感血凝素纳米颗粒的疫苗进行单次免疫可产生持久的保护性免疫。


接种疫苗是对抗流感的最有效策略。理想情况下，单剂疫苗会诱导有效和持久的疫苗效应。在这里，我们设计了一种基于病毒样颗粒 （VLP） 的疫苗，展示了来自 A/Puerto Rico/8/1934 （PR8HA-VLP） 的流感血凝素 （HA） 的多个拷贝，并检查了其在雪貂中的免疫原性和保护功效。接种单剂 PR8HA-VLP 后 3 周，有或没有佐剂，有效诱导针对同源病毒的血清中和抗体。当用同源病毒攻击单一免疫的雪貂时，病毒在鼻粘膜中的复制显着减少。血清滴度的长期监测显示，在用 PR8HA-VLP 佐剂接种后，中和抗体在接种疫苗后 20 至 183 周保留在相似水平，尽管在接种疫苗后 4 至 8 周观察到滴度下降 3 至 20 倍。在大多数动物中，第一次免疫后 183 周的加强免疫比初始免疫后 3 周产生的中和抗体滴度更高。这些结果证实，基于纳米颗粒的疫苗是一种很有前途的方法，可以有效引发针对流感病毒的持久多年中和抗体反应。