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An FcRn-targeted mucosal vaccine against SARS-CoV-2 infection and transmission
SARS-CoV-2 is primarily transmitted through droplets and airborne aerosols, and in order to prevent infection and reduce viral spread vaccines should elicit protective immunity in the airways. The neonatal Fc receptor (FcRn) transfers IgG across epithelial barriers and can enhance mucosal delivery o...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628175/ https://www.ncbi.nlm.nih.gov/pubmed/37932271 http://dx.doi.org/10.1038/s41467-023-42796-0 |
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author | Li, Weizhong Wang, Tao Rajendrakumar, Arunraj M. Acharya, Gyanada Miao, Zizhen Varghese, Berin P. Yu, Hailiang Dhakal, Bibek LeRoith, Tanya Karunakaran, Athira Tuo, Wenbin Zhu, Xiaoping |
author_facet | Li, Weizhong Wang, Tao Rajendrakumar, Arunraj M. Acharya, Gyanada Miao, Zizhen Varghese, Berin P. Yu, Hailiang Dhakal, Bibek LeRoith, Tanya Karunakaran, Athira Tuo, Wenbin Zhu, Xiaoping |
author_sort | Li, Weizhong |
collection | PubMed |
description | SARS-CoV-2 is primarily transmitted through droplets and airborne aerosols, and in order to prevent infection and reduce viral spread vaccines should elicit protective immunity in the airways. The neonatal Fc receptor (FcRn) transfers IgG across epithelial barriers and can enhance mucosal delivery of antigens. Here we explore FcRn-mediated respiratory delivery of SARS-CoV-2 spike (S). A monomeric IgG Fc was fused to a stabilized spike; the resulting S-Fc bound to S-specific antibodies and FcRn. Intranasal immunization of mice with S-Fc and CpG significantly induced antibody responses compared to the vaccination with S alone or PBS. Furthermore, we intranasally immunized mice or hamsters with S-Fc. A significant reduction of virus replication in nasal turbinate, lung, and brain was observed following nasal challenges with SARS-CoV-2 and its variants. Intranasal immunization also significantly reduced viral airborne transmission in hamsters. Nasal IgA, neutralizing antibodies, lung-resident memory T cells, and bone-marrow S-specific plasma cells mediated protection. Hence, FcRn delivers an S-Fc antigen effectively into the airway and induces protection against SARS-CoV-2 infection and transmission. |
format | Online Article Text |
id | pubmed-10628175 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-106281752023-11-08 An FcRn-targeted mucosal vaccine against SARS-CoV-2 infection and transmission Li, Weizhong Wang, Tao Rajendrakumar, Arunraj M. Acharya, Gyanada Miao, Zizhen Varghese, Berin P. Yu, Hailiang Dhakal, Bibek LeRoith, Tanya Karunakaran, Athira Tuo, Wenbin Zhu, Xiaoping Nat Commun Article SARS-CoV-2 is primarily transmitted through droplets and airborne aerosols, and in order to prevent infection and reduce viral spread vaccines should elicit protective immunity in the airways. The neonatal Fc receptor (FcRn) transfers IgG across epithelial barriers and can enhance mucosal delivery of antigens. Here we explore FcRn-mediated respiratory delivery of SARS-CoV-2 spike (S). A monomeric IgG Fc was fused to a stabilized spike; the resulting S-Fc bound to S-specific antibodies and FcRn. Intranasal immunization of mice with S-Fc and CpG significantly induced antibody responses compared to the vaccination with S alone or PBS. Furthermore, we intranasally immunized mice or hamsters with S-Fc. A significant reduction of virus replication in nasal turbinate, lung, and brain was observed following nasal challenges with SARS-CoV-2 and its variants. Intranasal immunization also significantly reduced viral airborne transmission in hamsters. Nasal IgA, neutralizing antibodies, lung-resident memory T cells, and bone-marrow S-specific plasma cells mediated protection. Hence, FcRn delivers an S-Fc antigen effectively into the airway and induces protection against SARS-CoV-2 infection and transmission. Nature Publishing Group UK 2023-11-06 /pmc/articles/PMC10628175/ /pubmed/37932271 http://dx.doi.org/10.1038/s41467-023-42796-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Li, Weizhong Wang, Tao Rajendrakumar, Arunraj M. Acharya, Gyanada Miao, Zizhen Varghese, Berin P. Yu, Hailiang Dhakal, Bibek LeRoith, Tanya Karunakaran, Athira Tuo, Wenbin Zhu, Xiaoping An FcRn-targeted mucosal vaccine against SARS-CoV-2 infection and transmission |
title | An FcRn-targeted mucosal vaccine against SARS-CoV-2 infection and transmission |
title_full | An FcRn-targeted mucosal vaccine against SARS-CoV-2 infection and transmission |
title_fullStr | An FcRn-targeted mucosal vaccine against SARS-CoV-2 infection and transmission |
title_full_unstemmed | An FcRn-targeted mucosal vaccine against SARS-CoV-2 infection and transmission |
title_short | An FcRn-targeted mucosal vaccine against SARS-CoV-2 infection and transmission |
title_sort | fcrn-targeted mucosal vaccine against sars-cov-2 infection and transmission |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628175/ https://www.ncbi.nlm.nih.gov/pubmed/37932271 http://dx.doi.org/10.1038/s41467-023-42796-0 |
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