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

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

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) s...

Full description

Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2020-07-01
Series:Vaccines
Subjects:
universal influenza vaccine
HA-stem antigen
capsid-like particles
Virus-like particles
trimer display
IgG2a
Online Access:https://www.mdpi.com/2076-393X/8/3/389
id doaj-db844abcf32c44f6b247988759fd368f
record_format Article
spelling doaj-db844abcf32c44f6b247988759fd368f2020-11-25T03:32:35ZengMDPI AGVaccines2076-393X2020-07-01838938910.3390/vaccines8030389A Vaccine Displaying a Trimeric Influenza-A HA Stem Protein on Capsid-Like Particles Elicits Potent and Long-Lasting Protection in MiceSusan Thrane0Kara-Lee Aves1Ida E. M Uddbäck2Christoph M. Janitzek3Julianna Han4Yuhe R. Yang5Andrew B. Ward6Thor G. Theander7Morten A. Nielsen8Ali Salanti9Allan R. Thomsen10Jan P. Christensen11Adam F. Sander12Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, DenmarkDepartment of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, DenmarkDepartment of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, DenmarkDepartment of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, DenmarkDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USADepartment of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, DenmarkDepartment of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, DenmarkDepartment of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, DenmarkDepartment of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, DenmarkDepartment of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, DenmarkDepartment of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, DenmarkDue 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<sub>stem</sub> trimer displayed on the surface of rigid capsid-like particles (CLP). Compared to soluble unconjugated HA<sub>stem</sub> trimer, the CLP-HA<sub>stem</sub> 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.https://www.mdpi.com/2076-393X/8/3/389universal influenza vaccineHA-stem antigencapsid-like particlesVirus-like particlestrimer displayIgG2a
collection DOAJ
language English
format Article
sources DOAJ
author 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
spellingShingle 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
A Vaccine Displaying a Trimeric Influenza-A HA Stem Protein on Capsid-Like Particles Elicits Potent and Long-Lasting Protection in Mice
Vaccines
universal influenza vaccine
HA-stem antigen
capsid-like particles
Virus-like particles
trimer display
IgG2a
author_facet 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
author_sort Susan Thrane
title A Vaccine Displaying a Trimeric Influenza-A HA Stem Protein on Capsid-Like Particles Elicits Potent and Long-Lasting Protection in Mice
title_short A Vaccine Displaying a Trimeric Influenza-A HA Stem Protein on Capsid-Like Particles Elicits Potent and Long-Lasting Protection in Mice
title_full A Vaccine Displaying a Trimeric Influenza-A HA Stem Protein on Capsid-Like Particles Elicits Potent and Long-Lasting Protection in Mice
title_fullStr A Vaccine Displaying a Trimeric Influenza-A HA Stem Protein on Capsid-Like Particles Elicits Potent and Long-Lasting Protection in Mice
title_full_unstemmed A Vaccine Displaying a Trimeric Influenza-A HA Stem Protein on Capsid-Like Particles Elicits Potent and Long-Lasting Protection in Mice
title_sort vaccine displaying a trimeric influenza-a ha stem protein on capsid-like particles elicits potent and long-lasting protection in mice
publisher MDPI AG
series Vaccines
issn 2076-393X
publishDate 2020-07-01
description 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<sub>stem</sub> trimer displayed on the surface of rigid capsid-like particles (CLP). Compared to soluble unconjugated HA<sub>stem</sub> trimer, the CLP-HA<sub>stem</sub> 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.
topic universal influenza vaccine
HA-stem antigen
capsid-like particles
Virus-like particles
trimer display
IgG2a
url https://www.mdpi.com/2076-393X/8/3/389
work_keys_str_mv AT susanthrane avaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
AT karaleeaves avaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
AT idaemuddback avaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
AT christophmjanitzek avaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
AT juliannahan avaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
AT yuheryang avaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
AT andrewbward avaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
AT thorgtheander avaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
AT mortenanielsen avaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
AT alisalanti avaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
AT allanrthomsen avaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
AT janpchristensen avaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
AT adamfsander avaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
AT susanthrane vaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
AT karaleeaves vaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
AT idaemuddback vaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
AT christophmjanitzek vaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
AT juliannahan vaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
AT yuheryang vaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
AT andrewbward vaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
AT thorgtheander vaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
AT mortenanielsen vaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
AT alisalanti vaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
AT allanrthomsen vaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
AT janpchristensen vaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
AT adamfsander vaccinedisplayingatrimericinfluenzaahastemproteinoncapsidlikeparticleselicitspotentandlonglastingprotectioninmice
_version_ 1724567360129466368

Similar Items