A Vaccine Displaying a Trimeric Influenza-A HA Stem Protein on Capsid-Like Particles Elicits Potent and Long-Lasting Protection in Mice

在衣壳状颗粒上展示三聚体甲型流感 HA 干蛋白的疫苗可在小鼠中产生强效且持久的保护作用

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作者:Susan Thrane, Kara-Lee Aves, Ida E M Uddbäck, Christoph M Janitzek, Julianna Han, Yuhe R Yang, Andrew B Ward, Thor G Theander, Morten A Nielsen, Ali Salanti, Allan R Thomsen, Jan P Christensen, Adam F Sander

Abstract

Due to constant antigenic drift and shift, current influenza-A vaccines need to be redesigned and administered annually. A universal flu vaccine (UFV) that provides long-lasting protection against both seasonal and emerging pandemic influenza strains is thus urgently needed. The hemagglutinin (HA) stem antigen is a promising target for such a vaccine as it contains neutralizing epitopes, known to induce cross-protective IgG responses against a wide variety of influenza subtypes. In this study, we describe the development of a UFV candidate consisting of a HAstem trimer displayed on the surface of rigid capsid-like particles (CLP). Compared to soluble unconjugated HAstem trimer, the CLP-HAstem particles induced a more potent, long-lasting immune response and were able to protect mice against both homologous and heterologous H1N1 influenza challenge, even after a single dose.

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