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Designed nanoparticles elicit cross-reactive antibody responses to conserved influenza virus hemagglutinin stem epitopes

Despite the availability of seasonal vaccines and antiviral medications, influenza virus continues to be a major health concern and pandemic threat due to the continually changing antigenic regions of the major surface glycoprotein, hemagglutinin (HA). One emerging strategy for the development of mo...

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Autores principales: McCraw, Dustin M., Myers, Mallory L., Gulati, Neetu M., Prabhakaran, Madhu, Brand, Joshua, Andrews, Sarah, Gallagher, John R., Maldonado-Puga, Samantha, Kim, Alexander J., Torian, Udana, Syeda, Hubza, Boyoglu-Barnum, Seyhan, Kanekiyo, Masaru, McDermott, Adrian B., Harris, Audray K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491405/
https://www.ncbi.nlm.nih.gov/pubmed/37639457
http://dx.doi.org/10.1371/journal.ppat.1011514
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author McCraw, Dustin M.
Myers, Mallory L.
Gulati, Neetu M.
Prabhakaran, Madhu
Brand, Joshua
Andrews, Sarah
Gallagher, John R.
Maldonado-Puga, Samantha
Kim, Alexander J.
Torian, Udana
Syeda, Hubza
Boyoglu-Barnum, Seyhan
Kanekiyo, Masaru
McDermott, Adrian B.
Harris, Audray K.
author_facet McCraw, Dustin M.
Myers, Mallory L.
Gulati, Neetu M.
Prabhakaran, Madhu
Brand, Joshua
Andrews, Sarah
Gallagher, John R.
Maldonado-Puga, Samantha
Kim, Alexander J.
Torian, Udana
Syeda, Hubza
Boyoglu-Barnum, Seyhan
Kanekiyo, Masaru
McDermott, Adrian B.
Harris, Audray K.
author_sort McCraw, Dustin M.
collection PubMed
description Despite the availability of seasonal vaccines and antiviral medications, influenza virus continues to be a major health concern and pandemic threat due to the continually changing antigenic regions of the major surface glycoprotein, hemagglutinin (HA). One emerging strategy for the development of more efficacious seasonal and universal influenza vaccines is structure-guided design of nanoparticles that display conserved regions of HA, such as the stem. Using the H1 HA subtype to establish proof of concept, we found that tandem copies of an alpha-helical fragment from the conserved stem region (helix-A) can be displayed on the protruding spikes structures of a capsid scaffold. The stem region of HA on these designed chimeric nanoparticles is immunogenic and the nanoparticles are biochemically robust in that heat exposure did not destroy the particles and immunogenicity was retained. Furthermore, mice vaccinated with H1-nanoparticles were protected from lethal challenge with H1N1 influenza virus. By using a nanoparticle library approach with this helix-A nanoparticle design, we show that this vaccine nanoparticle construct design could be applicable to different influenza HA subtypes. Importantly, antibodies elicited by H1, H5, and H7 nanoparticles demonstrated homosubtypic and heterosubtypic cross-reactivity binding to different HA subtypes. Also, helix-A nanoparticle immunizations were used to isolate mouse monoclonal antibodies that demonstrated heterosubtypic cross-reactivity and provided protection to mice from viral challenge via passive-transfer. This tandem helix-A nanoparticle construct represents a novel design to display several hundred copies of non-trimeric conserved HA stem epitopes on vaccine nanoparticles. This design concept provides a new approach to universal influenza vaccine development strategies and opens opportunities for the development of nanoparticles with broad coverage over many antigenically diverse influenza HA subtypes.
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spelling pubmed-104914052023-09-09 Designed nanoparticles elicit cross-reactive antibody responses to conserved influenza virus hemagglutinin stem epitopes McCraw, Dustin M. Myers, Mallory L. Gulati, Neetu M. Prabhakaran, Madhu Brand, Joshua Andrews, Sarah Gallagher, John R. Maldonado-Puga, Samantha Kim, Alexander J. Torian, Udana Syeda, Hubza Boyoglu-Barnum, Seyhan Kanekiyo, Masaru McDermott, Adrian B. Harris, Audray K. PLoS Pathog Research Article Despite the availability of seasonal vaccines and antiviral medications, influenza virus continues to be a major health concern and pandemic threat due to the continually changing antigenic regions of the major surface glycoprotein, hemagglutinin (HA). One emerging strategy for the development of more efficacious seasonal and universal influenza vaccines is structure-guided design of nanoparticles that display conserved regions of HA, such as the stem. Using the H1 HA subtype to establish proof of concept, we found that tandem copies of an alpha-helical fragment from the conserved stem region (helix-A) can be displayed on the protruding spikes structures of a capsid scaffold. The stem region of HA on these designed chimeric nanoparticles is immunogenic and the nanoparticles are biochemically robust in that heat exposure did not destroy the particles and immunogenicity was retained. Furthermore, mice vaccinated with H1-nanoparticles were protected from lethal challenge with H1N1 influenza virus. By using a nanoparticle library approach with this helix-A nanoparticle design, we show that this vaccine nanoparticle construct design could be applicable to different influenza HA subtypes. Importantly, antibodies elicited by H1, H5, and H7 nanoparticles demonstrated homosubtypic and heterosubtypic cross-reactivity binding to different HA subtypes. Also, helix-A nanoparticle immunizations were used to isolate mouse monoclonal antibodies that demonstrated heterosubtypic cross-reactivity and provided protection to mice from viral challenge via passive-transfer. This tandem helix-A nanoparticle construct represents a novel design to display several hundred copies of non-trimeric conserved HA stem epitopes on vaccine nanoparticles. This design concept provides a new approach to universal influenza vaccine development strategies and opens opportunities for the development of nanoparticles with broad coverage over many antigenically diverse influenza HA subtypes. Public Library of Science 2023-08-28 /pmc/articles/PMC10491405/ /pubmed/37639457 http://dx.doi.org/10.1371/journal.ppat.1011514 Text en https://creativecommons.org/publicdomain/zero/1.0/This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
McCraw, Dustin M.
Myers, Mallory L.
Gulati, Neetu M.
Prabhakaran, Madhu
Brand, Joshua
Andrews, Sarah
Gallagher, John R.
Maldonado-Puga, Samantha
Kim, Alexander J.
Torian, Udana
Syeda, Hubza
Boyoglu-Barnum, Seyhan
Kanekiyo, Masaru
McDermott, Adrian B.
Harris, Audray K.
Designed nanoparticles elicit cross-reactive antibody responses to conserved influenza virus hemagglutinin stem epitopes
title Designed nanoparticles elicit cross-reactive antibody responses to conserved influenza virus hemagglutinin stem epitopes
title_full Designed nanoparticles elicit cross-reactive antibody responses to conserved influenza virus hemagglutinin stem epitopes
title_fullStr Designed nanoparticles elicit cross-reactive antibody responses to conserved influenza virus hemagglutinin stem epitopes
title_full_unstemmed Designed nanoparticles elicit cross-reactive antibody responses to conserved influenza virus hemagglutinin stem epitopes
title_short Designed nanoparticles elicit cross-reactive antibody responses to conserved influenza virus hemagglutinin stem epitopes
title_sort designed nanoparticles elicit cross-reactive antibody responses to conserved influenza virus hemagglutinin stem epitopes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491405/
https://www.ncbi.nlm.nih.gov/pubmed/37639457
http://dx.doi.org/10.1371/journal.ppat.1011514
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