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...
Main Authors: | , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2020-07-01
|
Series: | Vaccines |
Subjects: | |
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 |