mRNA-1273 protects against SARS-CoV-2 beta infection in nonhuman primates

Kizzmekia S. Corbett; Anne P. Werner; Sarah O’ Connell; Matthew Gagne; Lilin Lai; Juan I. Moliva; Barbara Flynn; Angela Choi; Matthew Koch; Kathryn E. Foulds; Shayne F. Andrew; Dillon R. Flebbe; Evan Lamb; Saule T. Nurmukhambetova; Samantha J. Provost; Kevin W. Bock; Mahnaz Minai; Bianca M. Nagata; Alex Van Ry; Zackery Flinchbaugh; Timothy S. Johnston; Elham Bayat Mokhtari; Prakriti Mudvari; Amy R. Henry; Farida Laboune; Becky Chang; Maciel Porto; Jaclyn Wear; Gabriela S. Alvarado; Seyhan Boyoglu-Barnum; John Paul M. Todd; Bridget Bart; Anthony Cook; Alan Dodson; Laurent Pessaint; Katelyn Steingrebe; Sayda Elbashir; Manjari Sriparna; Andrew Pekosz; Hanne Andersen; Kai Wu; Darin K. Edwards; Swagata Kar; Mark G. Lewis; Eli Boritz; Ian N. Moore; Andrea Carfi; Mehul S. Suthar; Adrian McDermott; Mario Roederer; Martha C. Nason; Nancy J. Sullivan; Daniel C. Douek; Barney S. Graham; Robert A. Seder

doi:10.1038/s41590-021-01021-0

mRNA-1273 protects against SARS-CoV-2 beta infection in nonhuman primates

Kizzmekia S. Corbett, Anne P. Werner, Sarah O’ Connell, Matthew Gagne, Lilin Lai, Juan I. Moliva, Barbara Flynn, Angela Choi, Matthew Koch, Kathryn E. Foulds, Shayne F. Andrew, Dillon R. Flebbe, Evan Lamb, Saule T. Nurmukhambetova, Samantha J. Provost, Kevin W. Bock, Mahnaz Minai, Bianca M. Nagata, Alex Van Ry, Zackery FlinchbaughTimothy S. Johnston, Elham Bayat Mokhtari, Prakriti Mudvari, Amy R. Henry, Farida Laboune, Becky Chang, Maciel Porto, Jaclyn Wear, Gabriela S. Alvarado, Seyhan Boyoglu-Barnum, John Paul M. Todd, Bridget Bart, Anthony Cook, Alan Dodson, Laurent Pessaint, Katelyn Steingrebe, Sayda Elbashir, Manjari Sriparna, Andrew Pekosz, Hanne Andersen, Kai Wu, Darin K. Edwards, Swagata Kar, Mark G. Lewis, Eli Boritz, Ian N. Moore, Andrea Carfi, Mehul S. Suthar, Adrian McDermott, Mario Roederer, Martha C. Nason, Nancy J. Sullivan, Daniel C. Douek, Barney S. Graham, Robert A. Seder

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37 Scopus citations

Abstract

B.1.351 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant most resistant to antibody neutralization. We demonstrate how the dose and number of immunizations influence protection. Nonhuman primates 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 50% inhibitory reciprocal serum dilution neutralizing antibody titers against live SARS-CoV-2 p.Asp614Gly 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. After challenge with B.1.351, there was ~4- to 5-log₁₀ reduction of viral subgenomic RNA and low to undetectable replication in bronchoalveolar lavages in the two-dose vaccine groups, with a 1-log₁₀ reduction in nasal swabs in the 100-µg 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.

Original language	English
Pages (from-to)	1306-1315
Number of pages	10
Journal	Nature Immunology
Volume	22
Issue number	10
DOIs	https://doi.org/10.1038/s41590-021-01021-0
State	Published - Oct 2021
Externally published	Yes

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Corbett, K. S., Werner, A. P., Connell, S. O., Gagne, M., Lai, L., Moliva, J. I., Flynn, B., Choi, A., Koch, M., Foulds, K. E., Andrew, S. F., Flebbe, D. R., Lamb, E., Nurmukhambetova, S. T., Provost, S. J., Bock, K. W., Minai, M., Nagata, B. M., Ry, A. V., ... Seder, R. A. (2021). mRNA-1273 protects against SARS-CoV-2 beta infection in nonhuman primates. Nature Immunology, 22(10), 1306-1315. https://doi.org/10.1038/s41590-021-01021-0

@article{36ae70585e94471e9281c7767001791c,

title = "mRNA-1273 protects against SARS-CoV-2 beta infection in nonhuman primates",

abstract = "B.1.351 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant most resistant to antibody neutralization. We demonstrate how the dose and number of immunizations influence protection. Nonhuman primates received two doses of 30 or 100 µg of Moderna{\textquoteright}s mRNA-1273 vaccine, a single immunization of 30 µg, or no vaccine. Two doses of 100 µg of mRNA-1273 induced 50% inhibitory reciprocal serum dilution neutralizing antibody titers against live SARS-CoV-2 p.Asp614Gly 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. After challenge with B.1.351, there was ~4- to 5-log10 reduction of viral subgenomic RNA and low to undetectable replication in bronchoalveolar lavages in the two-dose vaccine groups, with a 1-log10 reduction in nasal swabs in the 100-µg 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.",

author = "Corbett, {Kizzmekia S.} and Werner, {Anne P.} and Connell, {Sarah O{\textquoteright}} and Matthew Gagne and Lilin Lai and Moliva, {Juan I.} and Barbara Flynn and Angela Choi and Matthew Koch and Foulds, {Kathryn E.} and Andrew, {Shayne F.} and Flebbe, {Dillon R.} and Evan Lamb and Nurmukhambetova, {Saule T.} and Provost, {Samantha J.} and Bock, {Kevin W.} and Mahnaz Minai and Nagata, {Bianca M.} and Ry, {Alex Van} and Zackery Flinchbaugh and Johnston, {Timothy S.} and Mokhtari, {Elham Bayat} and Prakriti Mudvari and Henry, {Amy R.} and Farida Laboune and Becky Chang and Maciel Porto and Jaclyn Wear and Alvarado, {Gabriela S.} and Seyhan Boyoglu-Barnum and Todd, {John Paul M.} and Bridget Bart and Anthony Cook and Alan Dodson and Laurent Pessaint and Katelyn Steingrebe and Sayda Elbashir and Manjari Sriparna and Andrew Pekosz and Hanne Andersen and Kai Wu and Edwards, {Darin K.} and Swagata Kar and Lewis, {Mark G.} and Eli Boritz and Moore, {Ian N.} and Andrea Carfi and Suthar, {Mehul S.} and Adrian McDermott and Mario Roederer and Nason, {Martha C.} and Sullivan, {Nancy J.} and Douek, {Daniel C.} and Graham, {Barney S.} and Seder, {Robert A.}",

note = "Publisher Copyright: {\textcopyright} 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.",

year = "2021",

month = oct,

doi = "10.1038/s41590-021-01021-0",

language = "English",

volume = "22",

pages = "1306--1315",

journal = "Nature Immunology",

issn = "1529-2908",

publisher = "Nature Publishing Group",

number = "10",

}

Corbett, KS, Werner, AP, Connell, SO, Gagne, M, Lai, L, Moliva, JI, Flynn, B, Choi, A, Koch, M, Foulds, KE, Andrew, SF, Flebbe, DR, Lamb, E, Nurmukhambetova, ST, Provost, SJ, Bock, KW, Minai, M, Nagata, BM, Ry, AV, Flinchbaugh, Z, Johnston, TS, Mokhtari, EB, Mudvari, P, Henry, AR, Laboune, F, Chang, B, Porto, M, Wear, J, Alvarado, GS, Boyoglu-Barnum, S, Todd, JPM, Bart, B, Cook, A, Dodson, A, Pessaint, L, Steingrebe, K, Elbashir, S, Sriparna, M, Pekosz, A, Andersen, H, Wu, K, Edwards, DK, Kar, S, Lewis, MG, Boritz, E, Moore, IN, Carfi, A, Suthar, MS, McDermott, A, Roederer, M, Nason, MC, Sullivan, NJ, Douek, DC, Graham, BS & Seder, RA 2021, 'mRNA-1273 protects against SARS-CoV-2 beta infection in nonhuman primates', Nature Immunology, vol. 22, no. 10, pp. 1306-1315. https://doi.org/10.1038/s41590-021-01021-0

TY - JOUR

T1 - mRNA-1273 protects against SARS-CoV-2 beta infection in nonhuman primates

AU - Corbett, Kizzmekia S.

AU - Werner, Anne P.

AU - Connell, Sarah O’

AU - Gagne, Matthew

AU - Lai, Lilin

AU - Moliva, Juan I.

AU - Flynn, Barbara

AU - Choi, Angela

AU - Koch, Matthew

AU - Foulds, Kathryn E.

AU - Andrew, Shayne F.

AU - Flebbe, Dillon R.

AU - Lamb, Evan

AU - Nurmukhambetova, Saule T.

AU - Provost, Samantha J.

AU - Bock, Kevin W.

AU - Minai, Mahnaz

AU - Nagata, Bianca M.

AU - Ry, Alex Van

AU - Flinchbaugh, Zackery

AU - Johnston, Timothy S.

AU - Mokhtari, Elham Bayat

AU - Mudvari, Prakriti

AU - Henry, Amy R.

AU - Laboune, Farida

AU - Chang, Becky

AU - Porto, Maciel

AU - Wear, Jaclyn

AU - Alvarado, Gabriela S.

AU - Boyoglu-Barnum, Seyhan

AU - Todd, John Paul M.

AU - Bart, Bridget

AU - Cook, Anthony

AU - Dodson, Alan

AU - Pessaint, Laurent

AU - Steingrebe, Katelyn

AU - Elbashir, Sayda

AU - Sriparna, Manjari

AU - Pekosz, Andrew

AU - Andersen, Hanne

AU - Wu, Kai

AU - Edwards, Darin K.

AU - Kar, Swagata

AU - Lewis, Mark G.

AU - Boritz, Eli

AU - Moore, Ian N.

AU - Carfi, Andrea

AU - Suthar, Mehul S.

AU - McDermott, Adrian

AU - Roederer, Mario

AU - Nason, Martha C.

AU - Sullivan, Nancy J.

AU - Douek, Daniel C.

AU - Graham, Barney S.

AU - Seder, Robert A.

PY - 2021/10

Y1 - 2021/10

N2 - B.1.351 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant most resistant to antibody neutralization. We demonstrate how the dose and number of immunizations influence protection. Nonhuman primates 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 50% inhibitory reciprocal serum dilution neutralizing antibody titers against live SARS-CoV-2 p.Asp614Gly 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. After challenge with B.1.351, there was ~4- to 5-log10 reduction of viral subgenomic RNA and low to undetectable replication in bronchoalveolar lavages in the two-dose vaccine groups, with a 1-log10 reduction in nasal swabs in the 100-µg 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.

AB - B.1.351 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant most resistant to antibody neutralization. We demonstrate how the dose and number of immunizations influence protection. Nonhuman primates 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 50% inhibitory reciprocal serum dilution neutralizing antibody titers against live SARS-CoV-2 p.Asp614Gly 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. After challenge with B.1.351, there was ~4- to 5-log10 reduction of viral subgenomic RNA and low to undetectable replication in bronchoalveolar lavages in the two-dose vaccine groups, with a 1-log10 reduction in nasal swabs in the 100-µg 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.

UR - http://www.scopus.com/inward/record.url?scp=85113224128&partnerID=8YFLogxK

U2 - 10.1038/s41590-021-01021-0

DO - 10.1038/s41590-021-01021-0

M3 - Article

C2 - 34417590

AN - SCOPUS:85113224128

SN - 1529-2908

VL - 22

SP - 1306

EP - 1315

JO - Nature Immunology

JF - Nature Immunology

IS - 10

ER -

mRNA-1273 protects against SARS-CoV-2 beta infection in nonhuman primates

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