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Construction, characterization, and immunization of nanoparticles that display a diverse array of influenza HA trimers

Current influenza vaccines do not elicit broadly protective immune responses against multiple strains. New strategies to focus the humoral immune response to conserved regions on influenza antigens are therefore required for recognition by broadly neutralizing antibodies. It has been suggested that...

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Autores principales: Cohen, Alexander A., Yang, Zhi, Gnanapragasam, Priyanthi N. P., Ou, Susan, Dam, Kim-Marie A., Wang, Haoqing, Bjorkman, Pamela J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932532/
https://www.ncbi.nlm.nih.gov/pubmed/33661993
http://dx.doi.org/10.1371/journal.pone.0247963
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author Cohen, Alexander A.
Yang, Zhi
Gnanapragasam, Priyanthi N. P.
Ou, Susan
Dam, Kim-Marie A.
Wang, Haoqing
Bjorkman, Pamela J.
author_facet Cohen, Alexander A.
Yang, Zhi
Gnanapragasam, Priyanthi N. P.
Ou, Susan
Dam, Kim-Marie A.
Wang, Haoqing
Bjorkman, Pamela J.
author_sort Cohen, Alexander A.
collection PubMed
description Current influenza vaccines do not elicit broadly protective immune responses against multiple strains. New strategies to focus the humoral immune response to conserved regions on influenza antigens are therefore required for recognition by broadly neutralizing antibodies. It has been suggested that B-cells with receptors that recognize conserved epitopes would be preferentially stimulated through avidity effects by mosaic particles presenting multiple forms of a variable antigen. We adapted SpyCatcher-based platforms, AP205 virus-like particles (VLPs) and mi3 nanoparticles (NPs), to covalently co-display SpyTagged hemagglutinin (HA) trimers from group 1 and group 2 influenza A strains. Here we show successful homotypic and heterotypic conjugation of up to 8 different HA trimers to both VLPs and NPs. We characterized the HA-VLPs and HA-NPs by cryo-electron tomography to derive the average number of conjugated HAs and their separation distances on particles, and compared immunizations of mosaic and homotypic particles in wild-type mice. Both types of HA particles elicited strong antibody responses, but the mosaic particles did not consistently elicit broader immune responses than mixtures of homotypic particles. We conclude that covalent attachment of HAs from currently-circulating influenza strains represents a viable alternative to current annual influenza vaccine strategies, but in the absence of further modifications, is unlikely to represent a method for making a universal influenza vaccine.
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spelling pubmed-79325322021-03-15 Construction, characterization, and immunization of nanoparticles that display a diverse array of influenza HA trimers Cohen, Alexander A. Yang, Zhi Gnanapragasam, Priyanthi N. P. Ou, Susan Dam, Kim-Marie A. Wang, Haoqing Bjorkman, Pamela J. PLoS One Research Article Current influenza vaccines do not elicit broadly protective immune responses against multiple strains. New strategies to focus the humoral immune response to conserved regions on influenza antigens are therefore required for recognition by broadly neutralizing antibodies. It has been suggested that B-cells with receptors that recognize conserved epitopes would be preferentially stimulated through avidity effects by mosaic particles presenting multiple forms of a variable antigen. We adapted SpyCatcher-based platforms, AP205 virus-like particles (VLPs) and mi3 nanoparticles (NPs), to covalently co-display SpyTagged hemagglutinin (HA) trimers from group 1 and group 2 influenza A strains. Here we show successful homotypic and heterotypic conjugation of up to 8 different HA trimers to both VLPs and NPs. We characterized the HA-VLPs and HA-NPs by cryo-electron tomography to derive the average number of conjugated HAs and their separation distances on particles, and compared immunizations of mosaic and homotypic particles in wild-type mice. Both types of HA particles elicited strong antibody responses, but the mosaic particles did not consistently elicit broader immune responses than mixtures of homotypic particles. We conclude that covalent attachment of HAs from currently-circulating influenza strains represents a viable alternative to current annual influenza vaccine strategies, but in the absence of further modifications, is unlikely to represent a method for making a universal influenza vaccine. Public Library of Science 2021-03-04 /pmc/articles/PMC7932532/ /pubmed/33661993 http://dx.doi.org/10.1371/journal.pone.0247963 Text en © 2021 Cohen et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Cohen, Alexander A.
Yang, Zhi
Gnanapragasam, Priyanthi N. P.
Ou, Susan
Dam, Kim-Marie A.
Wang, Haoqing
Bjorkman, Pamela J.
Construction, characterization, and immunization of nanoparticles that display a diverse array of influenza HA trimers
title Construction, characterization, and immunization of nanoparticles that display a diverse array of influenza HA trimers
title_full Construction, characterization, and immunization of nanoparticles that display a diverse array of influenza HA trimers
title_fullStr Construction, characterization, and immunization of nanoparticles that display a diverse array of influenza HA trimers
title_full_unstemmed Construction, characterization, and immunization of nanoparticles that display a diverse array of influenza HA trimers
title_short Construction, characterization, and immunization of nanoparticles that display a diverse array of influenza HA trimers
title_sort construction, characterization, and immunization of nanoparticles that display a diverse array of influenza ha trimers
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932532/
https://www.ncbi.nlm.nih.gov/pubmed/33661993
http://dx.doi.org/10.1371/journal.pone.0247963
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