Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates

Kizzmekia S. Corbett; Martha C. Nason; Britta Flach; Matthew Gagne; Sarah O'Connell; Timothy S. Johnston; Shruti N. Shah; Venkata Viswanadh Edara; Katharine Floyd; Lilin Lai; Charlene McDanal; Joseph R. Francica; Barbara Flynn; Kai Wu; Angela Choi; Matthew Koch; Olubukola M. Abiona; Anne P. Werner; Juan I. Moliva; Shayne F. Andrew; Mitzi M. Donaldson; Jonathan Fintzi; Dillon R. Flebbe; Evan Lamb; Amy T. Noe; Saule T. Nurmukhambetova; Samantha J. Provost; Anthony Cook; Alan Dodson; Andrew Faudree; Jack Greenhouse; Swagata Kar; Laurent Pessaint; Maciel Porto; Katelyn Steingrebe; Daniel Valentin; Serge Zouantcha; Kevin W. Bock; Mahnaz Minai; Bianca M. Nagata; Renee van de Wetering; Seyhan Boyoglu-Barnum; Kwanyee Leung; Wei Shi; Eun Sung Yang; Yi Zhang; John Paul M. Todd; Lingshu Wang; Gabriela S. Alvarado; Hanne Andersen; Kathryn E. Foulds; Darin K. Edwards; John R. Mascola; Ian N. Moore; Mark G. Lewis; Andrea Carfi; David Montefiori; Mehul S. Suthar; Adrian McDermott; Mario Roederer; Nancy J. Sullivan; Daniel C. Douek; Barney S. Graham; Robert A. Seder

doi:10.1126/science.abj0299

Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates

Kizzmekia S. Corbett, Martha C. Nason, Britta Flach, Matthew Gagne, Sarah O'Connell, Timothy S. Johnston, Shruti N. Shah, Venkata Viswanadh Edara, Katharine Floyd, Lilin Lai, Charlene McDanal, Joseph R. Francica, Barbara Flynn, Kai Wu, Angela Choi, Matthew Koch, Olubukola M. Abiona, Anne P. Werner, Juan I. Moliva, Shayne F. AndrewMitzi M. Donaldson, Jonathan Fintzi, Dillon R. Flebbe, Evan Lamb, Amy T. Noe, Saule T. Nurmukhambetova, Samantha J. Provost, Anthony Cook, Alan Dodson, Andrew Faudree, Jack Greenhouse, Swagata Kar, Laurent Pessaint, Maciel Porto, Katelyn Steingrebe, Daniel Valentin, Serge Zouantcha, Kevin W. Bock, Mahnaz Minai, Bianca M. Nagata, Renee van de Wetering, Seyhan Boyoglu-Barnum, Kwanyee Leung, Wei Shi, Eun Sung Yang, Yi Zhang, John Paul M. Todd, Lingshu Wang, Gabriela S. Alvarado, Hanne Andersen, Kathryn E. Foulds, Darin K. Edwards, John R. Mascola, Ian N. Moore, Mark G. Lewis, Andrea Carfi, David Montefiori, Mehul S. Suthar, Adrian McDermott, Mario Roederer, Nancy J. Sullivan, Daniel C. Douek, Barney S. Graham, Robert A. Seder

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198 Scopus citations

Abstract

Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. Here, nonhuman primates (NHPs) received either no vaccine or doses ranging from 0.3 to 100 mg of the mRNA-1273 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. mRNA-1273 vaccination elicited circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs after SARS-CoV-2 challenge in vaccinated animals and most strongly correlated with levels of anti-S antibody and neutralizing activity. Lower antibody levels were needed for reduction of viral replication in the lower airway than in the upper airway. Passive transfer of mRNA-1273-induced immunoglobulin G to naïve hamsters was sufficient to mediate protection. Thus, mRNA-1273 vaccine-induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 in NHPs.

Original language	English
Article number	eabj0299
Journal	Science
Volume	373
Issue number	6561
DOIs	https://doi.org/10.1126/science.abj0299
State	Published - 17 Sep 2021
Externally published	Yes

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Corbett, K. S., Nason, M. C., Flach, B., Gagne, M., O'Connell, S., Johnston, T. S., Shah, S. N., Edara, V. V., Floyd, K., Lai, L., McDanal, C., Francica, J. R., Flynn, B., Wu, K., Choi, A., Koch, M., Abiona, O. M., Werner, A. P., Moliva, J. I., ... Seder, R. A. (2021). Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. Science, 373(6561), Article eabj0299. https://doi.org/10.1126/science.abj0299

@article{b1f38198e05a4e54a530281033637783,

title = "Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates",

abstract = "Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. Here, nonhuman primates (NHPs) received either no vaccine or doses ranging from 0.3 to 100 mg of the mRNA-1273 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. mRNA-1273 vaccination elicited circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs after SARS-CoV-2 challenge in vaccinated animals and most strongly correlated with levels of anti-S antibody and neutralizing activity. Lower antibody levels were needed for reduction of viral replication in the lower airway than in the upper airway. Passive transfer of mRNA-1273-induced immunoglobulin G to na{\"i}ve hamsters was sufficient to mediate protection. Thus, mRNA-1273 vaccine-induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 in NHPs.",

author = "Corbett, {Kizzmekia S.} and Nason, {Martha C.} and Britta Flach and Matthew Gagne and Sarah O'Connell and Johnston, {Timothy S.} and Shah, {Shruti N.} and Edara, {Venkata Viswanadh} and Katharine Floyd and Lilin Lai and Charlene McDanal and Francica, {Joseph R.} and Barbara Flynn and Kai Wu and Angela Choi and Matthew Koch and Abiona, {Olubukola M.} and Werner, {Anne P.} and Moliva, {Juan I.} and Andrew, {Shayne F.} and Donaldson, {Mitzi M.} and Jonathan Fintzi and Flebbe, {Dillon R.} and Evan Lamb and Noe, {Amy T.} and Nurmukhambetova, {Saule T.} and Provost, {Samantha J.} and Anthony Cook and Alan Dodson and Andrew Faudree and Jack Greenhouse and Swagata Kar and Laurent Pessaint and Maciel Porto and Katelyn Steingrebe and Daniel Valentin and Serge Zouantcha and Bock, {Kevin W.} and Mahnaz Minai and Nagata, {Bianca M.} and {van de Wetering}, Renee and Seyhan Boyoglu-Barnum and Kwanyee Leung and Wei Shi and Yang, {Eun Sung} and Yi Zhang and Todd, {John Paul M.} and Lingshu Wang and Alvarado, {Gabriela S.} and Hanne Andersen and Foulds, {Kathryn E.} and Edwards, {Darin K.} and Mascola, {John R.} and Moore, {Ian N.} and Lewis, {Mark G.} and Andrea Carfi and David Montefiori and Suthar, {Mehul S.} and Adrian McDermott and Mario Roederer and Sullivan, {Nancy J.} and Douek, {Daniel C.} and Graham, {Barney S.} and Seder, {Robert A.}",

year = "2021",

month = sep,

day = "17",

doi = "10.1126/science.abj0299",

language = "English",

volume = "373",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6561",

}

Corbett, KS, Nason, MC, Flach, B, Gagne, M, O'Connell, S, Johnston, TS, Shah, SN, Edara, VV, Floyd, K, Lai, L, McDanal, C, Francica, JR, Flynn, B, Wu, K, Choi, A, Koch, M, Abiona, OM, Werner, AP, Moliva, JI, Andrew, SF, Donaldson, MM, Fintzi, J, Flebbe, DR, Lamb, E, Noe, AT, Nurmukhambetova, ST, Provost, SJ, Cook, A, Dodson, A, Faudree, A, Greenhouse, J, Kar, S, Pessaint, L, Porto, M, Steingrebe, K, Valentin, D, Zouantcha, S, Bock, KW, Minai, M, Nagata, BM, van de Wetering, R, Boyoglu-Barnum, S, Leung, K, Shi, W, Yang, ES, Zhang, Y, Todd, JPM, Wang, L, Alvarado, GS, Andersen, H, Foulds, KE, Edwards, DK, Mascola, JR, Moore, IN, Lewis, MG, Carfi, A, Montefiori, D, Suthar, MS, McDermott, A, Roederer, M, Sullivan, NJ, Douek, DC, Graham, BS & Seder, RA 2021, 'Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates', Science, vol. 373, no. 6561, eabj0299. https://doi.org/10.1126/science.abj0299

TY - JOUR

T1 - Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates

AU - Corbett, Kizzmekia S.

AU - Nason, Martha C.

AU - Flach, Britta

AU - Gagne, Matthew

AU - O'Connell, Sarah

AU - Johnston, Timothy S.

AU - Shah, Shruti N.

AU - Edara, Venkata Viswanadh

AU - Floyd, Katharine

AU - Lai, Lilin

AU - McDanal, Charlene

AU - Francica, Joseph R.

AU - Flynn, Barbara

AU - Wu, Kai

AU - Choi, Angela

AU - Koch, Matthew

AU - Abiona, Olubukola M.

AU - Werner, Anne P.

AU - Moliva, Juan I.

AU - Andrew, Shayne F.

AU - Donaldson, Mitzi M.

AU - Fintzi, Jonathan

AU - Flebbe, Dillon R.

AU - Lamb, Evan

AU - Noe, Amy T.

AU - Nurmukhambetova, Saule T.

AU - Provost, Samantha J.

AU - Cook, Anthony

AU - Dodson, Alan

AU - Faudree, Andrew

AU - Greenhouse, Jack

AU - Kar, Swagata

AU - Pessaint, Laurent

AU - Porto, Maciel

AU - Steingrebe, Katelyn

AU - Valentin, Daniel

AU - Zouantcha, Serge

AU - Bock, Kevin W.

AU - Minai, Mahnaz

AU - Nagata, Bianca M.

AU - van de Wetering, Renee

AU - Boyoglu-Barnum, Seyhan

AU - Leung, Kwanyee

AU - Shi, Wei

AU - Yang, Eun Sung

AU - Zhang, Yi

AU - Todd, John Paul M.

AU - Wang, Lingshu

AU - Alvarado, Gabriela S.

AU - Andersen, Hanne

AU - Foulds, Kathryn E.

AU - Edwards, Darin K.

AU - Mascola, John R.

AU - Moore, Ian N.

AU - Lewis, Mark G.

AU - Carfi, Andrea

AU - Montefiori, David

AU - Suthar, Mehul S.

AU - McDermott, Adrian

AU - Roederer, Mario

AU - Sullivan, Nancy J.

AU - Douek, Daniel C.

AU - Graham, Barney S.

AU - Seder, Robert A.

PY - 2021/9/17

Y1 - 2021/9/17

N2 - Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. Here, nonhuman primates (NHPs) received either no vaccine or doses ranging from 0.3 to 100 mg of the mRNA-1273 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. mRNA-1273 vaccination elicited circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs after SARS-CoV-2 challenge in vaccinated animals and most strongly correlated with levels of anti-S antibody and neutralizing activity. Lower antibody levels were needed for reduction of viral replication in the lower airway than in the upper airway. Passive transfer of mRNA-1273-induced immunoglobulin G to naïve hamsters was sufficient to mediate protection. Thus, mRNA-1273 vaccine-induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 in NHPs.

AB - Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. Here, nonhuman primates (NHPs) received either no vaccine or doses ranging from 0.3 to 100 mg of the mRNA-1273 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. mRNA-1273 vaccination elicited circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs after SARS-CoV-2 challenge in vaccinated animals and most strongly correlated with levels of anti-S antibody and neutralizing activity. Lower antibody levels were needed for reduction of viral replication in the lower airway than in the upper airway. Passive transfer of mRNA-1273-induced immunoglobulin G to naïve hamsters was sufficient to mediate protection. Thus, mRNA-1273 vaccine-induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 in NHPs.

UR - http://www.scopus.com/inward/record.url?scp=85112723038&partnerID=8YFLogxK

U2 - 10.1126/science.abj0299

DO - 10.1126/science.abj0299

M3 - Article

C2 - 34529476

AN - SCOPUS:85112723038

SN - 0036-8075

VL - 373

JO - Science

JF - Science

IS - 6561

M1 - eabj0299

ER -

Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates

Abstract

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