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

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

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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.

Original language	English
Article number	389
Journal	Vaccines
Volume	8
Issue number	3
ISSN	2076-393X
DOIs	https://doi.org/10.3390/vaccines8030389
Publication status	Published - 2020

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10.3390/vaccines8030389Licence: CC BY

A Vaccine Displaying a Trimeric Influenza-A HA Stem Protein on Capsid-Like Particles Elicits Potent and Long-Lasting Protection in MiceFinal published version, 5.06 MBLicence: CC BY

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Thrane, S., Aves, K.-L., Uddbäck, I. E. M., Janitzek, C. M., Han, J., Yang, Y. R., Ward, A. B., Theander, T. G., Nielsen, M. A., Salanti, A., Thomsen, A. R., Christensen, J. P., & Sander, A. F. (2020). A vaccine displaying a trimeric influenza-A HA stem protein on capsid-like particles elicits potent and long-lasting protection in mice. Vaccines, 8(3), Article 389. https://doi.org/10.3390/vaccines8030389

Thrane, S, Aves, K-L , Uddbäck, IEM, Janitzek, CM, Han, J, Yang, YR, Ward, AB, Theander, TG , Nielsen, MA , Salanti, A , Thomsen, AR , Christensen, JP & Sander, AF 2020, 'A vaccine displaying a trimeric influenza-A HA stem protein on capsid-like particles elicits potent and long-lasting protection in mice', Vaccines, vol. 8, no. 3, 389. https://doi.org/10.3390/vaccines8030389

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title = "A vaccine displaying a trimeric influenza-A HA stem protein on capsid-like particles elicits potent and long-lasting protection in mice",

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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AU - Thrane, Susan

AU - Aves, Kara-Lee

AU - Uddbäck, Ida E M

AU - Janitzek, Christoph M

AU - Han, Julianna

AU - Yang, Yuhe R

AU - Ward, Andrew B

AU - Theander, Thor G

AU - Nielsen, Morten A

AU - Salanti, Ali

AU - Thomsen, Allan R

AU - Christensen, Jan P

AU - Sander, Adam F

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N2 - 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.

AB - 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.

U2 - 10.3390/vaccines8030389

DO - 10.3390/vaccines8030389

M3 - Journal article

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SN - 2076-393X

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