Chiba Shiho, Maemura Tadashi, Loeffler Kathryn, Frey Steven J, Gu Chunyang, Biswas Asim, Hatta Masato, Kawaoka Yoshihiro, Kane Ravi S
Department of Pathobiological Sciences, School of Veterinary Medicine Influenza Research Institute, University of Wisconsin-Madison Madison Wisconsin USA.
Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA) The University of Tokyo Tokyo Japan.
Bioeng Transl Med. 2024 Jun 3;9(5):e10689. doi: 10.1002/btm2.10689. eCollection 2024 Sep.
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.
接种疫苗是对抗流感最有效的策略。理想情况下，单剂量疫苗就能诱导出强大且持久的疫苗效果。在此，我们设计了一种基于病毒样颗粒（VLP）的疫苗，该疫苗展示了来自A/波多黎各/8/1934（PR8HA-VLP）的多个流感血凝素（HA）拷贝，并在雪貂中检测了其免疫原性和保护效力。在接种单剂量PR8HA-VLP（有无佐剂）3周后，血清中和抗体能有效诱导产生，针对同源病毒。当对接种过一次的雪貂进行同源病毒攻击时，鼻黏膜中的病毒复制显著减少。血清滴度的长期监测显示，在用PR8HA-VLP佐剂接种疫苗后，接种后20至183周中和抗体维持在相似水平，尽管在接种后3至20周观察到滴度下降了4至8倍。在首次免疫183周后进行加强免疫，在大多数动物中诱导出的中和抗体滴度高于初次免疫3周后的滴度。这些结果证实，基于纳米颗粒的疫苗是有效诱导针对流感病毒的持久多年中和抗体反应的一种有前景的方法。
