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

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.

Originalsprog	Engelsk
Tidsskrift	Vaccines
Vol/bind	8
Udgave nummer	3
ISSN	2076-393X
DOI	https://doi.org/10.3390/vaccines8030389
Status	Udgivet - 15 jul. 2020

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10.3390/vaccines8030389

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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). 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.",

author = "Susan Thrane and Kara-Lee Aves and Uddb{\"a}ck, {Ida E M} and Janitzek, {Christoph M} and Julianna Han and Yang, {Yuhe R} and Ward, {Andrew B} and Theander, {Thor G} and Nielsen, {Morten A} and Ali Salanti and Thomsen, {Allan R} and Christensen, {Jan P} and Sander, {Adam F}",

year = "2020",

month = jul,

day = "15",

doi = "10.3390/vaccines8030389",

language = "English",

volume = "8",

journal = "Vaccines",

issn = "2076-393X",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

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TY - JOUR

T1 - A Vaccine Displaying a Trimeric Influenza-A HA Stem Protein on Capsid-Like Particles Elicits Potent and Long-Lasting Protection in Mice

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

PY - 2020/7/15

Y1 - 2020/7/15

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

C2 - 32679905

SN - 2076-393X

VL - 8

JO - Vaccines

JF - Vaccines

IS - 3

ER -

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

Abstract

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