Conformational modulation of influenza virus hemagglutinin: characterization and in vivo efficacy of monomeric form

Abstract Mutational changes that mostly occur at the head region of hemagglutinin (HA) lead to the emergence of new epidemic influenza viruses, whereas HA antigens have been modified to generate broadly neutralizing antibodies toward highly conserved epitopes in the HA stem. Interestingly, a recent...

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Autores principales:	Jong Hyeon Seok, Jeongwon Kim, Dan Bi Lee, Ki Joon Cho, Ji-Hye Lee, Garam Bae, Mi Sook Chung, Kyung Hyun Kim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/08f959aac7f047e7af6edc81ca70b117
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spelling	oai:doaj.org-article:08f959aac7f047e7af6edc81ca70b1172021-12-02T16:07:59ZConformational modulation of influenza virus hemagglutinin: characterization and in vivo efficacy of monomeric form10.1038/s41598-017-08021-x2045-2322https://doaj.org/article/08f959aac7f047e7af6edc81ca70b1172017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08021-xhttps://doaj.org/toc/2045-2322Abstract Mutational changes that mostly occur at the head region of hemagglutinin (HA) lead to the emergence of new epidemic influenza viruses, whereas HA antigens have been modified to generate broadly neutralizing antibodies toward highly conserved epitopes in the HA stem. Interestingly, a recent analysis of serum antibody repertoires showed that broadly neutralizing antibodies bind to HA monomer at a conserved region occluded at the intermonomer interface of HA trimer and confer protection in animal models. We showed previously that the recombinant HA ectodomain from a pandemic strain A/Korea/01/2009 was monomeric in solution and crystal structure. In order to examine the potential antigenicity of a monomeric form, we designed HA monomer that incorporates mutations to destabilize trimer conformations. Starting with the HA trimer from a seasonal strain A/Thailand/CU44/2006, mutations were introduced at the intermonomer interface, Ser199 of HA1 and Gly47, Arg75, Phe88, Val91, and Arg106 of HA2. Two mutants, F88E and V91W, were characterized to form a monomer and their double mutant F88E/V91W monomer was selected as an antigen. Animal studies showed that the HA monomer induced protective immunity in vivo, comparable to the trimer, albeit low antibody titers in sera.Jong Hyeon SeokJeongwon KimDan Bi LeeKi Joon ChoJi-Hye LeeGaram BaeMi Sook ChungKyung Hyun KimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jong Hyeon Seok Jeongwon Kim Dan Bi Lee Ki Joon Cho Ji-Hye Lee Garam Bae Mi Sook Chung Kyung Hyun Kim Conformational modulation of influenza virus hemagglutinin: characterization and in vivo efficacy of monomeric form
description	Abstract Mutational changes that mostly occur at the head region of hemagglutinin (HA) lead to the emergence of new epidemic influenza viruses, whereas HA antigens have been modified to generate broadly neutralizing antibodies toward highly conserved epitopes in the HA stem. Interestingly, a recent analysis of serum antibody repertoires showed that broadly neutralizing antibodies bind to HA monomer at a conserved region occluded at the intermonomer interface of HA trimer and confer protection in animal models. We showed previously that the recombinant HA ectodomain from a pandemic strain A/Korea/01/2009 was monomeric in solution and crystal structure. In order to examine the potential antigenicity of a monomeric form, we designed HA monomer that incorporates mutations to destabilize trimer conformations. Starting with the HA trimer from a seasonal strain A/Thailand/CU44/2006, mutations were introduced at the intermonomer interface, Ser199 of HA1 and Gly47, Arg75, Phe88, Val91, and Arg106 of HA2. Two mutants, F88E and V91W, were characterized to form a monomer and their double mutant F88E/V91W monomer was selected as an antigen. Animal studies showed that the HA monomer induced protective immunity in vivo, comparable to the trimer, albeit low antibody titers in sera.
format	article
author	Jong Hyeon Seok Jeongwon Kim Dan Bi Lee Ki Joon Cho Ji-Hye Lee Garam Bae Mi Sook Chung Kyung Hyun Kim
author_facet	Jong Hyeon Seok Jeongwon Kim Dan Bi Lee Ki Joon Cho Ji-Hye Lee Garam Bae Mi Sook Chung Kyung Hyun Kim
author_sort	Jong Hyeon Seok
title	Conformational modulation of influenza virus hemagglutinin: characterization and in vivo efficacy of monomeric form
title_short	Conformational modulation of influenza virus hemagglutinin: characterization and in vivo efficacy of monomeric form
title_full	Conformational modulation of influenza virus hemagglutinin: characterization and in vivo efficacy of monomeric form
title_fullStr	Conformational modulation of influenza virus hemagglutinin: characterization and in vivo efficacy of monomeric form
title_full_unstemmed	Conformational modulation of influenza virus hemagglutinin: characterization and in vivo efficacy of monomeric form
title_sort	conformational modulation of influenza virus hemagglutinin: characterization and in vivo efficacy of monomeric form
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/08f959aac7f047e7af6edc81ca70b117
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Conformational modulation of influenza virus hemagglutinin: characterization and in vivo efficacy of monomeric form

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