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mRNA-1273 Protects against SARS-CoV-2 Beta Infection in Nonhuman Primates

B.1.351 is the SARS-CoV-2 variant most resistant to antibody neutralization. We demonstrate how the dose and number of immunizations influence protection. Nonhuman primates (NHP) received two doses of 30 or 100 μg of Moderna’s mRNA-1273 vaccine, a single immunization of 30 μg, or no vaccine. Two dos...

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Autores principales: Corbett, Kizzmekia S., Werner, Anne P., O’ Connell, Sarah, Gagne, Matthew, Lai, Lilin, Moliva, Juan I., Flynn, Barbara, Choi, Angela, Koch, Matthew, Foulds, Kathryn E., Andrew, Shayne F., Flebbe, Dillon R., Lamb, Evan, Nurmukhambetova, Saule T., Provost, Samantha J., Bock, Kevin W., Minai, Mahnaz, Nagata, Bianca M., Van Ry, Alex, Flinchbaugh, Zackery, Johnston, Timothy S., Mokhtari, Elham Bayat, Mudvari, Prakriti, Henry, Amy R., Laboune, Farida, Chang, Becky, Porto, Maciel, Wear, Jaclyn, Alvarado, Gabriela S., Boyoglu-Barnum, Seyhan, Todd, John-Paul M., Bart, Bridget, Cook, Anthony, Dodson, Alan, Pessaint, Laurent, Steingrebe, Katelyn, Elbashir, Sayda, Sriparna, Manjari, Pekosz, Andrew, Andersen, Hanne, Wu, Kai, Edwards, Darin K., Kar, Swagata, Lewis, Mark G., Boritz, Eli, Moore, Ian N., Carfi, Andrea, Suthar, Mehul S., McDermott, Adrian, Roederer, Mario, Nason, Martha C., Sullivan, Nancy J., Douek, Daniel C., Graham, Barney S., Seder, Robert A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488000/
https://www.ncbi.nlm.nih.gov/pubmed/34417590
http://dx.doi.org/10.1038/s41590-021-01021-0
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author Corbett, Kizzmekia S.
Werner, Anne P.
O’ Connell, Sarah
Gagne, Matthew
Lai, Lilin
Moliva, Juan I.
Flynn, Barbara
Choi, Angela
Koch, Matthew
Foulds, Kathryn E.
Andrew, Shayne F.
Flebbe, Dillon R.
Lamb, Evan
Nurmukhambetova, Saule T.
Provost, Samantha J.
Bock, Kevin W.
Minai, Mahnaz
Nagata, Bianca M.
Van Ry, Alex
Flinchbaugh, Zackery
Johnston, Timothy S.
Mokhtari, Elham Bayat
Mudvari, Prakriti
Henry, Amy R.
Laboune, Farida
Chang, Becky
Porto, Maciel
Wear, Jaclyn
Alvarado, Gabriela S.
Boyoglu-Barnum, Seyhan
Todd, John-Paul M.
Bart, Bridget
Cook, Anthony
Dodson, Alan
Pessaint, Laurent
Steingrebe, Katelyn
Elbashir, Sayda
Sriparna, Manjari
Pekosz, Andrew
Andersen, Hanne
Wu, Kai
Edwards, Darin K.
Kar, Swagata
Lewis, Mark G.
Boritz, Eli
Moore, Ian N.
Carfi, Andrea
Suthar, Mehul S.
McDermott, Adrian
Roederer, Mario
Nason, Martha C.
Sullivan, Nancy J.
Douek, Daniel C.
Graham, Barney S.
Seder, Robert A.
author_facet Corbett, Kizzmekia S.
Werner, Anne P.
O’ Connell, Sarah
Gagne, Matthew
Lai, Lilin
Moliva, Juan I.
Flynn, Barbara
Choi, Angela
Koch, Matthew
Foulds, Kathryn E.
Andrew, Shayne F.
Flebbe, Dillon R.
Lamb, Evan
Nurmukhambetova, Saule T.
Provost, Samantha J.
Bock, Kevin W.
Minai, Mahnaz
Nagata, Bianca M.
Van Ry, Alex
Flinchbaugh, Zackery
Johnston, Timothy S.
Mokhtari, Elham Bayat
Mudvari, Prakriti
Henry, Amy R.
Laboune, Farida
Chang, Becky
Porto, Maciel
Wear, Jaclyn
Alvarado, Gabriela S.
Boyoglu-Barnum, Seyhan
Todd, John-Paul M.
Bart, Bridget
Cook, Anthony
Dodson, Alan
Pessaint, Laurent
Steingrebe, Katelyn
Elbashir, Sayda
Sriparna, Manjari
Pekosz, Andrew
Andersen, Hanne
Wu, Kai
Edwards, Darin K.
Kar, Swagata
Lewis, Mark G.
Boritz, Eli
Moore, Ian N.
Carfi, Andrea
Suthar, Mehul S.
McDermott, Adrian
Roederer, Mario
Nason, Martha C.
Sullivan, Nancy J.
Douek, Daniel C.
Graham, Barney S.
Seder, Robert A.
author_sort Corbett, Kizzmekia S.
collection PubMed
description B.1.351 is the SARS-CoV-2 variant most resistant to antibody neutralization. We demonstrate how the dose and number of immunizations influence protection. Nonhuman primates (NHP) received two doses of 30 or 100 μg of Moderna’s mRNA-1273 vaccine, a single immunization of 30 μg, or no vaccine. Two doses of 100 μg of mRNA-1273 induced reciprocal ID(50) mean neutralizing antibody titers against live SARS-CoV-2 D614G and B.1.351 of 3,300 and 240, respectively. Higher neutralizing responses against B.1.617.2 were also observed after two doses compared to a single dose. Following challenge with B.1.351, there was ~4–5−log(10) reduction of viral subgenomic RNA (sgRNA) and low to undetectable replication in bronchoalveolar lavages in the two-dose vaccine groups, with a 1−log(10) reduction in nasal swabs (NS) in the 100 μg dose group. These data establish that a two-dose regimen of mRNA-1273 will be critical for providing upper and lower airway protection against major variants of concern.
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spelling pubmed-84880002022-02-20 mRNA-1273 Protects against SARS-CoV-2 Beta Infection in Nonhuman Primates Corbett, Kizzmekia S. Werner, Anne P. O’ Connell, Sarah Gagne, Matthew Lai, Lilin Moliva, Juan I. Flynn, Barbara Choi, Angela Koch, Matthew Foulds, Kathryn E. Andrew, Shayne F. Flebbe, Dillon R. Lamb, Evan Nurmukhambetova, Saule T. Provost, Samantha J. Bock, Kevin W. Minai, Mahnaz Nagata, Bianca M. Van Ry, Alex Flinchbaugh, Zackery Johnston, Timothy S. Mokhtari, Elham Bayat Mudvari, Prakriti Henry, Amy R. Laboune, Farida Chang, Becky Porto, Maciel Wear, Jaclyn Alvarado, Gabriela S. Boyoglu-Barnum, Seyhan Todd, John-Paul M. Bart, Bridget Cook, Anthony Dodson, Alan Pessaint, Laurent Steingrebe, Katelyn Elbashir, Sayda Sriparna, Manjari Pekosz, Andrew Andersen, Hanne Wu, Kai Edwards, Darin K. Kar, Swagata Lewis, Mark G. Boritz, Eli Moore, Ian N. Carfi, Andrea Suthar, Mehul S. McDermott, Adrian Roederer, Mario Nason, Martha C. Sullivan, Nancy J. Douek, Daniel C. Graham, Barney S. Seder, Robert A. Nat Immunol Article B.1.351 is the SARS-CoV-2 variant most resistant to antibody neutralization. We demonstrate how the dose and number of immunizations influence protection. Nonhuman primates (NHP) received two doses of 30 or 100 μg of Moderna’s mRNA-1273 vaccine, a single immunization of 30 μg, or no vaccine. Two doses of 100 μg of mRNA-1273 induced reciprocal ID(50) mean neutralizing antibody titers against live SARS-CoV-2 D614G and B.1.351 of 3,300 and 240, respectively. Higher neutralizing responses against B.1.617.2 were also observed after two doses compared to a single dose. Following challenge with B.1.351, there was ~4–5−log(10) reduction of viral subgenomic RNA (sgRNA) and low to undetectable replication in bronchoalveolar lavages in the two-dose vaccine groups, with a 1−log(10) reduction in nasal swabs (NS) in the 100 μg dose group. These data establish that a two-dose regimen of mRNA-1273 will be critical for providing upper and lower airway protection against major variants of concern. 2021-08-20 2021-10 /pmc/articles/PMC8488000/ /pubmed/34417590 http://dx.doi.org/10.1038/s41590-021-01021-0 Text en https://www.springernature.com/gp/open-research/policies/accepted-manuscript-termsUsers may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: https://www.springernature.com/gp/open-research/policies/accepted-manuscript-terms
spellingShingle Article
Corbett, Kizzmekia S.
Werner, Anne P.
O’ Connell, Sarah
Gagne, Matthew
Lai, Lilin
Moliva, Juan I.
Flynn, Barbara
Choi, Angela
Koch, Matthew
Foulds, Kathryn E.
Andrew, Shayne F.
Flebbe, Dillon R.
Lamb, Evan
Nurmukhambetova, Saule T.
Provost, Samantha J.
Bock, Kevin W.
Minai, Mahnaz
Nagata, Bianca M.
Van Ry, Alex
Flinchbaugh, Zackery
Johnston, Timothy S.
Mokhtari, Elham Bayat
Mudvari, Prakriti
Henry, Amy R.
Laboune, Farida
Chang, Becky
Porto, Maciel
Wear, Jaclyn
Alvarado, Gabriela S.
Boyoglu-Barnum, Seyhan
Todd, John-Paul M.
Bart, Bridget
Cook, Anthony
Dodson, Alan
Pessaint, Laurent
Steingrebe, Katelyn
Elbashir, Sayda
Sriparna, Manjari
Pekosz, Andrew
Andersen, Hanne
Wu, Kai
Edwards, Darin K.
Kar, Swagata
Lewis, Mark G.
Boritz, Eli
Moore, Ian N.
Carfi, Andrea
Suthar, Mehul S.
McDermott, Adrian
Roederer, Mario
Nason, Martha C.
Sullivan, Nancy J.
Douek, Daniel C.
Graham, Barney S.
Seder, Robert A.
mRNA-1273 Protects against SARS-CoV-2 Beta Infection in Nonhuman Primates
title mRNA-1273 Protects against SARS-CoV-2 Beta Infection in Nonhuman Primates
title_full mRNA-1273 Protects against SARS-CoV-2 Beta Infection in Nonhuman Primates
title_fullStr mRNA-1273 Protects against SARS-CoV-2 Beta Infection in Nonhuman Primates
title_full_unstemmed mRNA-1273 Protects against SARS-CoV-2 Beta Infection in Nonhuman Primates
title_short mRNA-1273 Protects against SARS-CoV-2 Beta Infection in Nonhuman Primates
title_sort mrna-1273 protects against sars-cov-2 beta infection in nonhuman primates
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488000/
https://www.ncbi.nlm.nih.gov/pubmed/34417590
http://dx.doi.org/10.1038/s41590-021-01021-0
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