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Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates
BACKGROUND: Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important to evaluate in nonhuman primates. METHODS: Nonhuman primates...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Massachusetts Medical Society
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449230/ https://www.ncbi.nlm.nih.gov/pubmed/32722908 http://dx.doi.org/10.1056/NEJMoa2024671 |
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author | Corbett, Kizzmekia S. Flynn, Barbara Foulds, Kathryn E. Francica, Joseph R. Boyoglu-Barnum, Seyhan Werner, Anne P. Flach, Britta O’Connell, Sarah Bock, Kevin W. Minai, Mahnaz Nagata, Bianca M. Andersen, Hanne Martinez, David R. Noe, Amy T. Douek, Naomi Donaldson, Mitzi M. Nji, Nadesh N. Alvarado, Gabriela S. Edwards, Darin K. Flebbe, Dillon R. Lamb, Evan Doria-Rose, Nicole A. Lin, Bob C. Louder, Mark K. O’Dell, Sijy Schmidt, Stephen D. Phung, Emily Chang, Lauren A. Yap, Christina Todd, John-Paul M. Pessaint, Laurent Van Ry, Alex Browne, Shanai Greenhouse, Jack Putman-Taylor, Tammy Strasbaugh, Amanda Campbell, Tracey-Ann Cook, Anthony Dodson, Alan Steingrebe, Katelyn Shi, Wei Zhang, Yi Abiona, Olubukola M. Wang, Lingshu Pegu, Amarendra Yang, Eun Sung Leung, Kwanyee Zhou, Tongqing Teng, I-Ting Widge, Alicia Gordon, Ingelise Novik, Laura Gillespie, Rebecca A. Loomis, Rebecca J. Moliva, Juan I. Stewart-Jones, Guillaume Himansu, Sunny Kong, Wing-Pui Nason, Martha C. Morabito, Kaitlyn M. Ruckwardt, Tracy J. Ledgerwood, Julie E. Gaudinski, Martin R. Kwong, Peter D. Mascola, John R. Carfi, Andrea Lewis, Mark G. Baric, Ralph S. McDermott, Adrian Moore, Ian N. Sullivan, Nancy J. Roederer, Mario Seder, Robert A. Graham, Barney S. |
author_facet | Corbett, Kizzmekia S. Flynn, Barbara Foulds, Kathryn E. Francica, Joseph R. Boyoglu-Barnum, Seyhan Werner, Anne P. Flach, Britta O’Connell, Sarah Bock, Kevin W. Minai, Mahnaz Nagata, Bianca M. Andersen, Hanne Martinez, David R. Noe, Amy T. Douek, Naomi Donaldson, Mitzi M. Nji, Nadesh N. Alvarado, Gabriela S. Edwards, Darin K. Flebbe, Dillon R. Lamb, Evan Doria-Rose, Nicole A. Lin, Bob C. Louder, Mark K. O’Dell, Sijy Schmidt, Stephen D. Phung, Emily Chang, Lauren A. Yap, Christina Todd, John-Paul M. Pessaint, Laurent Van Ry, Alex Browne, Shanai Greenhouse, Jack Putman-Taylor, Tammy Strasbaugh, Amanda Campbell, Tracey-Ann Cook, Anthony Dodson, Alan Steingrebe, Katelyn Shi, Wei Zhang, Yi Abiona, Olubukola M. Wang, Lingshu Pegu, Amarendra Yang, Eun Sung Leung, Kwanyee Zhou, Tongqing Teng, I-Ting Widge, Alicia Gordon, Ingelise Novik, Laura Gillespie, Rebecca A. Loomis, Rebecca J. Moliva, Juan I. Stewart-Jones, Guillaume Himansu, Sunny Kong, Wing-Pui Nason, Martha C. Morabito, Kaitlyn M. Ruckwardt, Tracy J. Ledgerwood, Julie E. Gaudinski, Martin R. Kwong, Peter D. Mascola, John R. Carfi, Andrea Lewis, Mark G. Baric, Ralph S. McDermott, Adrian Moore, Ian N. Sullivan, Nancy J. Roederer, Mario Seder, Robert A. Graham, Barney S. |
author_sort | Corbett, Kizzmekia S. |
collection | PubMed |
description | BACKGROUND: Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important to evaluate in nonhuman primates. METHODS: Nonhuman primates received 10 or 100 μg of mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein of SARS-CoV-2, or no vaccine. Antibody and T-cell responses were assessed before upper- and lower-airway challenge with SARS-CoV-2. Active viral replication and viral genomes in bronchoalveolar-lavage (BAL) fluid and nasal swab specimens were assessed by polymerase chain reaction, and histopathological analysis and viral quantification were performed on lung-tissue specimens. RESULTS: The mRNA-1273 vaccine candidate induced antibody levels exceeding those in human convalescent-phase serum, with live-virus reciprocal 50% inhibitory dilution (ID(50)) geometric mean titers of 501 in the 10-μg dose group and 3481 in the 100-μg dose group. Vaccination induced type 1 helper T-cell (Th1)–biased CD4 T-cell responses and low or undetectable Th2 or CD8 T-cell responses. Viral replication was not detectable in BAL fluid by day 2 after challenge in seven of eight animals in both vaccinated groups. No viral replication was detectable in the nose of any of the eight animals in the 100-μg dose group by day 2 after challenge, and limited inflammation or detectable viral genome or antigen was noted in lungs of animals in either vaccine group. CONCLUSIONS: Vaccination of nonhuman primates with mRNA-1273 induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung. (Funded by the National Institutes of Health and others.) |
format | Online Article Text |
id | pubmed-7449230 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Massachusetts Medical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-74492302020-08-27 Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates Corbett, Kizzmekia S. Flynn, Barbara Foulds, Kathryn E. Francica, Joseph R. Boyoglu-Barnum, Seyhan Werner, Anne P. Flach, Britta O’Connell, Sarah Bock, Kevin W. Minai, Mahnaz Nagata, Bianca M. Andersen, Hanne Martinez, David R. Noe, Amy T. Douek, Naomi Donaldson, Mitzi M. Nji, Nadesh N. Alvarado, Gabriela S. Edwards, Darin K. Flebbe, Dillon R. Lamb, Evan Doria-Rose, Nicole A. Lin, Bob C. Louder, Mark K. O’Dell, Sijy Schmidt, Stephen D. Phung, Emily Chang, Lauren A. Yap, Christina Todd, John-Paul M. Pessaint, Laurent Van Ry, Alex Browne, Shanai Greenhouse, Jack Putman-Taylor, Tammy Strasbaugh, Amanda Campbell, Tracey-Ann Cook, Anthony Dodson, Alan Steingrebe, Katelyn Shi, Wei Zhang, Yi Abiona, Olubukola M. Wang, Lingshu Pegu, Amarendra Yang, Eun Sung Leung, Kwanyee Zhou, Tongqing Teng, I-Ting Widge, Alicia Gordon, Ingelise Novik, Laura Gillespie, Rebecca A. Loomis, Rebecca J. Moliva, Juan I. Stewart-Jones, Guillaume Himansu, Sunny Kong, Wing-Pui Nason, Martha C. Morabito, Kaitlyn M. Ruckwardt, Tracy J. Ledgerwood, Julie E. Gaudinski, Martin R. Kwong, Peter D. Mascola, John R. Carfi, Andrea Lewis, Mark G. Baric, Ralph S. McDermott, Adrian Moore, Ian N. Sullivan, Nancy J. Roederer, Mario Seder, Robert A. Graham, Barney S. N Engl J Med Original Article BACKGROUND: Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important to evaluate in nonhuman primates. METHODS: Nonhuman primates received 10 or 100 μg of mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein of SARS-CoV-2, or no vaccine. Antibody and T-cell responses were assessed before upper- and lower-airway challenge with SARS-CoV-2. Active viral replication and viral genomes in bronchoalveolar-lavage (BAL) fluid and nasal swab specimens were assessed by polymerase chain reaction, and histopathological analysis and viral quantification were performed on lung-tissue specimens. RESULTS: The mRNA-1273 vaccine candidate induced antibody levels exceeding those in human convalescent-phase serum, with live-virus reciprocal 50% inhibitory dilution (ID(50)) geometric mean titers of 501 in the 10-μg dose group and 3481 in the 100-μg dose group. Vaccination induced type 1 helper T-cell (Th1)–biased CD4 T-cell responses and low or undetectable Th2 or CD8 T-cell responses. Viral replication was not detectable in BAL fluid by day 2 after challenge in seven of eight animals in both vaccinated groups. No viral replication was detectable in the nose of any of the eight animals in the 100-μg dose group by day 2 after challenge, and limited inflammation or detectable viral genome or antigen was noted in lungs of animals in either vaccine group. CONCLUSIONS: Vaccination of nonhuman primates with mRNA-1273 induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung. (Funded by the National Institutes of Health and others.) Massachusetts Medical Society 2020-07-28 /pmc/articles/PMC7449230/ /pubmed/32722908 http://dx.doi.org/10.1056/NEJMoa2024671 Text en Copyright © 2020 Massachusetts Medical Society. All rights reserved. This article is made available via the PMC Open Access Subset for unrestricted re-use, except commercial resale, and analyses in any form or by any means with acknowledgment of the original source. These permissions are granted for the duration of the Covid-19 pandemic or until revoked in writing. Upon expiration of these permissions, PMC is granted a license to make this article available via PMC and Europe PMC, subject to existing copyright protections. |
spellingShingle | Original Article Corbett, Kizzmekia S. Flynn, Barbara Foulds, Kathryn E. Francica, Joseph R. Boyoglu-Barnum, Seyhan Werner, Anne P. Flach, Britta O’Connell, Sarah Bock, Kevin W. Minai, Mahnaz Nagata, Bianca M. Andersen, Hanne Martinez, David R. Noe, Amy T. Douek, Naomi Donaldson, Mitzi M. Nji, Nadesh N. Alvarado, Gabriela S. Edwards, Darin K. Flebbe, Dillon R. Lamb, Evan Doria-Rose, Nicole A. Lin, Bob C. Louder, Mark K. O’Dell, Sijy Schmidt, Stephen D. Phung, Emily Chang, Lauren A. Yap, Christina Todd, John-Paul M. Pessaint, Laurent Van Ry, Alex Browne, Shanai Greenhouse, Jack Putman-Taylor, Tammy Strasbaugh, Amanda Campbell, Tracey-Ann Cook, Anthony Dodson, Alan Steingrebe, Katelyn Shi, Wei Zhang, Yi Abiona, Olubukola M. Wang, Lingshu Pegu, Amarendra Yang, Eun Sung Leung, Kwanyee Zhou, Tongqing Teng, I-Ting Widge, Alicia Gordon, Ingelise Novik, Laura Gillespie, Rebecca A. Loomis, Rebecca J. Moliva, Juan I. Stewart-Jones, Guillaume Himansu, Sunny Kong, Wing-Pui Nason, Martha C. Morabito, Kaitlyn M. Ruckwardt, Tracy J. Ledgerwood, Julie E. Gaudinski, Martin R. Kwong, Peter D. Mascola, John R. Carfi, Andrea Lewis, Mark G. Baric, Ralph S. McDermott, Adrian Moore, Ian N. Sullivan, Nancy J. Roederer, Mario Seder, Robert A. Graham, Barney S. Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates |
title | Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates |
title_full | Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates |
title_fullStr | Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates |
title_full_unstemmed | Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates |
title_short | Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates |
title_sort | evaluation of the mrna-1273 vaccine against sars-cov-2 in nonhuman primates |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449230/ https://www.ncbi.nlm.nih.gov/pubmed/32722908 http://dx.doi.org/10.1056/NEJMoa2024671 |
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