Cargando…

Identification of Antibodies Targeting the H3N2 Hemagglutinin Receptor Binding Site following Vaccination of Humans

Antibodies targeting the receptor binding site (RBS) of the influenza virus hemagglutinin (HA) protein are usually not broadly reactive because their footprints are typically large and extend to nearby variable HA residues. Here, we identify several human H3N2 HA RBS-targeting monoclonal antibodies...

Descripción completa

Detalles Bibliográficos
Autores principales: Zost, Seth J., Lee, Juhye, Gumina, Megan E., Parkhouse, Kaela, Henry, Carole, Wu, Nicholas C., Lee, Chang-Chun D., Wilson, Ian A., Wilson, Patrick C., Bloom, Jesse D., Hensley, Scott E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953393/
https://www.ncbi.nlm.nih.gov/pubmed/31875553
http://dx.doi.org/10.1016/j.celrep.2019.11.084
_version_ 1783486620836560896
author Zost, Seth J.
Lee, Juhye
Gumina, Megan E.
Parkhouse, Kaela
Henry, Carole
Wu, Nicholas C.
Lee, Chang-Chun D.
Wilson, Ian A.
Wilson, Patrick C.
Bloom, Jesse D.
Hensley, Scott E.
author_facet Zost, Seth J.
Lee, Juhye
Gumina, Megan E.
Parkhouse, Kaela
Henry, Carole
Wu, Nicholas C.
Lee, Chang-Chun D.
Wilson, Ian A.
Wilson, Patrick C.
Bloom, Jesse D.
Hensley, Scott E.
author_sort Zost, Seth J.
collection PubMed
description Antibodies targeting the receptor binding site (RBS) of the influenza virus hemagglutinin (HA) protein are usually not broadly reactive because their footprints are typically large and extend to nearby variable HA residues. Here, we identify several human H3N2 HA RBS-targeting monoclonal antibodies (mAbs) that are sensitive to substitutions in conventional antigenic sites and are therefore not broadly reactive. However, we also identify an H3N2 HA RBS-targeting mAb that is exceptionally broadly reactive despite being sensitive to substitutions in residues outside of the RBS. We show that similar antibodies are present at measurable levels in the sera of some individuals but that they are inefficiently elicited by conventional vaccines. Our data indicate that HA RBS-targeting antibodies can be effective against variable viral strains even when they are somewhat sensitive to substitutions in HA residues adjacent to the RBS.
format Online
Article
Text
id pubmed-6953393
institution National Center for Biotechnology Information
language English
publishDate 2019
record_format MEDLINE/PubMed
spelling pubmed-69533932020-01-10 Identification of Antibodies Targeting the H3N2 Hemagglutinin Receptor Binding Site following Vaccination of Humans Zost, Seth J. Lee, Juhye Gumina, Megan E. Parkhouse, Kaela Henry, Carole Wu, Nicholas C. Lee, Chang-Chun D. Wilson, Ian A. Wilson, Patrick C. Bloom, Jesse D. Hensley, Scott E. Cell Rep Article Antibodies targeting the receptor binding site (RBS) of the influenza virus hemagglutinin (HA) protein are usually not broadly reactive because their footprints are typically large and extend to nearby variable HA residues. Here, we identify several human H3N2 HA RBS-targeting monoclonal antibodies (mAbs) that are sensitive to substitutions in conventional antigenic sites and are therefore not broadly reactive. However, we also identify an H3N2 HA RBS-targeting mAb that is exceptionally broadly reactive despite being sensitive to substitutions in residues outside of the RBS. We show that similar antibodies are present at measurable levels in the sera of some individuals but that they are inefficiently elicited by conventional vaccines. Our data indicate that HA RBS-targeting antibodies can be effective against variable viral strains even when they are somewhat sensitive to substitutions in HA residues adjacent to the RBS. 2019-12-24 /pmc/articles/PMC6953393/ /pubmed/31875553 http://dx.doi.org/10.1016/j.celrep.2019.11.084 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Zost, Seth J.
Lee, Juhye
Gumina, Megan E.
Parkhouse, Kaela
Henry, Carole
Wu, Nicholas C.
Lee, Chang-Chun D.
Wilson, Ian A.
Wilson, Patrick C.
Bloom, Jesse D.
Hensley, Scott E.
Identification of Antibodies Targeting the H3N2 Hemagglutinin Receptor Binding Site following Vaccination of Humans
title Identification of Antibodies Targeting the H3N2 Hemagglutinin Receptor Binding Site following Vaccination of Humans
title_full Identification of Antibodies Targeting the H3N2 Hemagglutinin Receptor Binding Site following Vaccination of Humans
title_fullStr Identification of Antibodies Targeting the H3N2 Hemagglutinin Receptor Binding Site following Vaccination of Humans
title_full_unstemmed Identification of Antibodies Targeting the H3N2 Hemagglutinin Receptor Binding Site following Vaccination of Humans
title_short Identification of Antibodies Targeting the H3N2 Hemagglutinin Receptor Binding Site following Vaccination of Humans
title_sort identification of antibodies targeting the h3n2 hemagglutinin receptor binding site following vaccination of humans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953393/
https://www.ncbi.nlm.nih.gov/pubmed/31875553
http://dx.doi.org/10.1016/j.celrep.2019.11.084
work_keys_str_mv AT zostsethj identificationofantibodiestargetingtheh3n2hemagglutininreceptorbindingsitefollowingvaccinationofhumans
AT leejuhye identificationofantibodiestargetingtheh3n2hemagglutininreceptorbindingsitefollowingvaccinationofhumans
AT guminamegane identificationofantibodiestargetingtheh3n2hemagglutininreceptorbindingsitefollowingvaccinationofhumans
AT parkhousekaela identificationofantibodiestargetingtheh3n2hemagglutininreceptorbindingsitefollowingvaccinationofhumans
AT henrycarole identificationofantibodiestargetingtheh3n2hemagglutininreceptorbindingsitefollowingvaccinationofhumans
AT wunicholasc identificationofantibodiestargetingtheh3n2hemagglutininreceptorbindingsitefollowingvaccinationofhumans
AT leechangchund identificationofantibodiestargetingtheh3n2hemagglutininreceptorbindingsitefollowingvaccinationofhumans
AT wilsoniana identificationofantibodiestargetingtheh3n2hemagglutininreceptorbindingsitefollowingvaccinationofhumans
AT wilsonpatrickc identificationofantibodiestargetingtheh3n2hemagglutininreceptorbindingsitefollowingvaccinationofhumans
AT bloomjessed identificationofantibodiestargetingtheh3n2hemagglutininreceptorbindingsitefollowingvaccinationofhumans
AT hensleyscotte identificationofantibodiestargetingtheh3n2hemagglutininreceptorbindingsitefollowingvaccinationofhumans