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

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

doi:10.3390/vaccines8030389

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

Vaccines (Basel). 2020 Jul 15;8(3):389. doi: 10.3390/vaccines8030389.

Authors

Affiliations

¹ Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark.
² Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
³ AdaptVac Aps, Agern Alle 1, 2970 Hørsholm, Denmark.

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 HA_stem trimer displayed on the surface of rigid capsid-like particles (CLP). Compared to soluble unconjugated HA_stem trimer, the CLP-HA_stem 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.

Keywords: HA-stem antigen; IgG2a; Virus-like particles; capsid-like particles; pandemic preparedness; trimer display; universal influenza vaccine.

Abstract

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