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...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Nature Publishing Group
2017-08-01
|
Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-017-08021-x |
id |
doaj-08f959aac7f047e7af6edc81ca70b117 |
---|---|
record_format |
Article |
spelling |
doaj-08f959aac7f047e7af6edc81ca70b1172020-12-08T02:53:57ZengNature Publishing GroupScientific Reports2045-23222017-08-01711910.1038/s41598-017-08021-xConformational modulation of influenza virus hemagglutinin: characterization and in vivo efficacy of monomeric formJong Hyeon Seok0Jeongwon Kim1Dan Bi Lee2Ki Joon Cho3Ji-Hye Lee4Garam Bae5Mi Sook Chung6Kyung Hyun Kim7Department of Biotechnology & Bioinformatics, Korea UniversityDepartment of Food and Nutrition, Duksung Women’s UniversityDepartment of Biotechnology & Bioinformatics, Korea UniversityAntibody Engineering Team, Mogam InstituteDepartment of Biotechnology & Bioinformatics, Korea UniversityDepartment of Food and Nutrition, Duksung Women’s UniversityDepartment of Food and Nutrition, Duksung Women’s UniversityDepartment of Biotechnology & Bioinformatics, Korea UniversityAbstract 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.https://doi.org/10.1038/s41598-017-08021-x |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jong Hyeon Seok Jeongwon Kim Dan Bi Lee Ki Joon Cho Ji-Hye Lee Garam Bae Mi Sook Chung Kyung Hyun Kim |
spellingShingle |
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 Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-08-01 |
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. |
url |
https://doi.org/10.1038/s41598-017-08021-x |
work_keys_str_mv |
AT jonghyeonseok conformationalmodulationofinfluenzavirushemagglutinincharacterizationandinvivoefficacyofmonomericform AT jeongwonkim conformationalmodulationofinfluenzavirushemagglutinincharacterizationandinvivoefficacyofmonomericform AT danbilee conformationalmodulationofinfluenzavirushemagglutinincharacterizationandinvivoefficacyofmonomericform AT kijooncho conformationalmodulationofinfluenzavirushemagglutinincharacterizationandinvivoefficacyofmonomericform AT jihyelee conformationalmodulationofinfluenzavirushemagglutinincharacterizationandinvivoefficacyofmonomericform AT garambae conformationalmodulationofinfluenzavirushemagglutinincharacterizationandinvivoefficacyofmonomericform AT misookchung conformationalmodulationofinfluenzavirushemagglutinincharacterizationandinvivoefficacyofmonomericform AT kyunghyunkim conformationalmodulationofinfluenzavirushemagglutinincharacterizationandinvivoefficacyofmonomericform |
_version_ |
1724393166587559936 |