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Protective antibodies elicited by SARS-CoV-2 spike protein vaccination are boosted in the lung after challenge in nonhuman primates
Adjuvanted soluble protein vaccines have been used extensively in humans for protection against various viral infections based on their robust induction of antibody responses. Here, soluble prefusion-stabilized spike protein trimers (preS dTM) from severe acute respiratory syndrome coronavirus 2 (SA...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266840/ https://www.ncbi.nlm.nih.gov/pubmed/34315825 http://dx.doi.org/10.1126/scitranslmed.abi4547 |
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author | Francica, Joseph R. Flynn, Barbara J. Foulds, Kathryn E. Noe, Amy T. Werner, Anne P. Moore, Ian N. Gagne, Matthew Johnston, Timothy S. Tucker, Courtney Davis, Rachel L. Flach, Britta O’Connell, Sarah Andrew, Shayne F. Lamb, Evan Flebbe, Dillon R. Nurmukhambetova, Saule T. Donaldson, Mitzi M. Todd, John-Paul M. Zhu, Alex Lee Atyeo, Caroline Fischinger, Stephanie Gorman, Matthew J Shin, Sally Edara, Venkata Viswanadh Floyd, Katharine Lai, Lilin Boyoglu-Barnum, Seyhan Van De Wetering, Renee Tylor, Alida McCarthy, Elizabeth Lecouturier, Valerie Ruiz, Sophie Berry, Catherine Tibbitts, Timothy Andersen, Hanne Cook, Anthony Dodson, Alan Pessaint, Laurent Van Ry, Alex Koutsoukos, Marguerite Gutzeit, Cindy Teng, I.-Ting Zhou, Tongqing Li, Dapeng Haynes, Barton F. Kwong, Peter D. McDermott, Adrian Lewis, Mark G. Fu, Tong Ming Chicz, Roman van der Most, Robbert Corbett, Kizzmekia S. Suthar, Mehul S. Alter, Galit Roederer, Mario Sullivan, Nancy J. Douek, Daniel C. Graham, Barney S. Casimiro, Danilo Seder, Robert A. |
author_facet | Francica, Joseph R. Flynn, Barbara J. Foulds, Kathryn E. Noe, Amy T. Werner, Anne P. Moore, Ian N. Gagne, Matthew Johnston, Timothy S. Tucker, Courtney Davis, Rachel L. Flach, Britta O’Connell, Sarah Andrew, Shayne F. Lamb, Evan Flebbe, Dillon R. Nurmukhambetova, Saule T. Donaldson, Mitzi M. Todd, John-Paul M. Zhu, Alex Lee Atyeo, Caroline Fischinger, Stephanie Gorman, Matthew J Shin, Sally Edara, Venkata Viswanadh Floyd, Katharine Lai, Lilin Boyoglu-Barnum, Seyhan Van De Wetering, Renee Tylor, Alida McCarthy, Elizabeth Lecouturier, Valerie Ruiz, Sophie Berry, Catherine Tibbitts, Timothy Andersen, Hanne Cook, Anthony Dodson, Alan Pessaint, Laurent Van Ry, Alex Koutsoukos, Marguerite Gutzeit, Cindy Teng, I.-Ting Zhou, Tongqing Li, Dapeng Haynes, Barton F. Kwong, Peter D. McDermott, Adrian Lewis, Mark G. Fu, Tong Ming Chicz, Roman van der Most, Robbert Corbett, Kizzmekia S. Suthar, Mehul S. Alter, Galit Roederer, Mario Sullivan, Nancy J. Douek, Daniel C. Graham, Barney S. Casimiro, Danilo Seder, Robert A. |
author_sort | Francica, Joseph R. |
collection | PubMed |
description | Adjuvanted soluble protein vaccines have been used extensively in humans for protection against various viral infections based on their robust induction of antibody responses. Here, soluble prefusion-stabilized spike protein trimers (preS dTM) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were formulated with the adjuvant AS03 and administered twice to nonhuman primates (NHPs). Binding and functional neutralization assays and systems serology revealed that the vaccinated NHP developed AS03-dependent multifunctional humoral responses that targeted distinct domains of the spike protein and bound to a variety of Fc receptors mediating immune cell effector functions in vitro. The neutralizing 50% inhibitory concentration titers for pseudovirus and live SARS-CoV-2 were higher than titers for a panel of human convalescent serum samples. NHPs were challenged intranasally and intratracheally with a high dose (3 × 10(6) plaque forming units) of SARS-CoV-2 (USA-WA1/2020 isolate). Two days after challenge, vaccinated NHPs showed rapid control of viral replication in both the upper and lower airways. Vaccinated NHPs also had increased spike protein–specific immunoglobulin G (IgG) antibody responses in the lung as early as 2 days after challenge. Moreover, passive transfer of vaccine-induced IgG to hamsters mediated protection from subsequent SARS-CoV-2 challenge. These data show that antibodies induced by the AS03-adjuvanted preS dTM vaccine were sufficient to mediate protection against SARS-CoV-2 in NHPs and that rapid anamnestic antibody responses in the lung may be a key mechanism for protection. |
format | Online Article Text |
id | pubmed-9266840 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-92668402022-07-14 Protective antibodies elicited by SARS-CoV-2 spike protein vaccination are boosted in the lung after challenge in nonhuman primates Francica, Joseph R. Flynn, Barbara J. Foulds, Kathryn E. Noe, Amy T. Werner, Anne P. Moore, Ian N. Gagne, Matthew Johnston, Timothy S. Tucker, Courtney Davis, Rachel L. Flach, Britta O’Connell, Sarah Andrew, Shayne F. Lamb, Evan Flebbe, Dillon R. Nurmukhambetova, Saule T. Donaldson, Mitzi M. Todd, John-Paul M. Zhu, Alex Lee Atyeo, Caroline Fischinger, Stephanie Gorman, Matthew J Shin, Sally Edara, Venkata Viswanadh Floyd, Katharine Lai, Lilin Boyoglu-Barnum, Seyhan Van De Wetering, Renee Tylor, Alida McCarthy, Elizabeth Lecouturier, Valerie Ruiz, Sophie Berry, Catherine Tibbitts, Timothy Andersen, Hanne Cook, Anthony Dodson, Alan Pessaint, Laurent Van Ry, Alex Koutsoukos, Marguerite Gutzeit, Cindy Teng, I.-Ting Zhou, Tongqing Li, Dapeng Haynes, Barton F. Kwong, Peter D. McDermott, Adrian Lewis, Mark G. Fu, Tong Ming Chicz, Roman van der Most, Robbert Corbett, Kizzmekia S. Suthar, Mehul S. Alter, Galit Roederer, Mario Sullivan, Nancy J. Douek, Daniel C. Graham, Barney S. Casimiro, Danilo Seder, Robert A. Sci Transl Med Research Articles Adjuvanted soluble protein vaccines have been used extensively in humans for protection against various viral infections based on their robust induction of antibody responses. Here, soluble prefusion-stabilized spike protein trimers (preS dTM) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were formulated with the adjuvant AS03 and administered twice to nonhuman primates (NHPs). Binding and functional neutralization assays and systems serology revealed that the vaccinated NHP developed AS03-dependent multifunctional humoral responses that targeted distinct domains of the spike protein and bound to a variety of Fc receptors mediating immune cell effector functions in vitro. The neutralizing 50% inhibitory concentration titers for pseudovirus and live SARS-CoV-2 were higher than titers for a panel of human convalescent serum samples. NHPs were challenged intranasally and intratracheally with a high dose (3 × 10(6) plaque forming units) of SARS-CoV-2 (USA-WA1/2020 isolate). Two days after challenge, vaccinated NHPs showed rapid control of viral replication in both the upper and lower airways. Vaccinated NHPs also had increased spike protein–specific immunoglobulin G (IgG) antibody responses in the lung as early as 2 days after challenge. Moreover, passive transfer of vaccine-induced IgG to hamsters mediated protection from subsequent SARS-CoV-2 challenge. These data show that antibodies induced by the AS03-adjuvanted preS dTM vaccine were sufficient to mediate protection against SARS-CoV-2 in NHPs and that rapid anamnestic antibody responses in the lung may be a key mechanism for protection. American Association for the Advancement of Science 2021-08-18 2021-07-27 /pmc/articles/PMC9266840/ /pubmed/34315825 http://dx.doi.org/10.1126/scitranslmed.abi4547 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Francica, Joseph R. Flynn, Barbara J. Foulds, Kathryn E. Noe, Amy T. Werner, Anne P. Moore, Ian N. Gagne, Matthew Johnston, Timothy S. Tucker, Courtney Davis, Rachel L. Flach, Britta O’Connell, Sarah Andrew, Shayne F. Lamb, Evan Flebbe, Dillon R. Nurmukhambetova, Saule T. Donaldson, Mitzi M. Todd, John-Paul M. Zhu, Alex Lee Atyeo, Caroline Fischinger, Stephanie Gorman, Matthew J Shin, Sally Edara, Venkata Viswanadh Floyd, Katharine Lai, Lilin Boyoglu-Barnum, Seyhan Van De Wetering, Renee Tylor, Alida McCarthy, Elizabeth Lecouturier, Valerie Ruiz, Sophie Berry, Catherine Tibbitts, Timothy Andersen, Hanne Cook, Anthony Dodson, Alan Pessaint, Laurent Van Ry, Alex Koutsoukos, Marguerite Gutzeit, Cindy Teng, I.-Ting Zhou, Tongqing Li, Dapeng Haynes, Barton F. Kwong, Peter D. McDermott, Adrian Lewis, Mark G. Fu, Tong Ming Chicz, Roman van der Most, Robbert Corbett, Kizzmekia S. Suthar, Mehul S. Alter, Galit Roederer, Mario Sullivan, Nancy J. Douek, Daniel C. Graham, Barney S. Casimiro, Danilo Seder, Robert A. Protective antibodies elicited by SARS-CoV-2 spike protein vaccination are boosted in the lung after challenge in nonhuman primates |
title | Protective antibodies elicited by SARS-CoV-2 spike protein vaccination are boosted in the lung after challenge in nonhuman primates |
title_full | Protective antibodies elicited by SARS-CoV-2 spike protein vaccination are boosted in the lung after challenge in nonhuman primates |
title_fullStr | Protective antibodies elicited by SARS-CoV-2 spike protein vaccination are boosted in the lung after challenge in nonhuman primates |
title_full_unstemmed | Protective antibodies elicited by SARS-CoV-2 spike protein vaccination are boosted in the lung after challenge in nonhuman primates |
title_short | Protective antibodies elicited by SARS-CoV-2 spike protein vaccination are boosted in the lung after challenge in nonhuman primates |
title_sort | protective antibodies elicited by sars-cov-2 spike protein vaccination are boosted in the lung after challenge in nonhuman primates |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9266840/ https://www.ncbi.nlm.nih.gov/pubmed/34315825 http://dx.doi.org/10.1126/scitranslmed.abi4547 |
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