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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
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.
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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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