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mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits comparable B cell expansion, neutralizing antibodies and protection against Omicron

Matthew Gagne, Juan I. Moliva, Kathryn E. Foulds, Shayne F. Andrew, Barbara J. Flynn, Anne P. Werner, Danielle A. Wagner, I-Ting Teng, Bob C. Lin, Christopher Moore, Nazaire Jean-Baptiste, Robin Carroll, Stephanie L. Foster, Mit Patel, Madison Ellis, Venkata-Viswanadh Edara, Nahara Vargas Maldonado, Mahnaz Minai, Lauren McCormick, Christopher Cole Honeycutt, Bianca M. Nagata, Kevin W. Bock, Caitlyn N. M. Dulan, Jamilet Cordon, John-Paul M. Todd, Elizabeth McCarthy, Laurent Pessaint, Alex Van Ry, Brandon Narvaez, Daniel Valentin, Anthony Cook, Alan Dodson, Katelyn Steingrebe, Dillon R. Flebbe, Saule T. Nurmukhambetova, Sucheta Godbole, Amy R. Henry, Farida Laboune, Jesmine Roberts-Torres, Cynthia G. Lorang, Shivani Amin, Jessica Trost, Mursal Naisan, Manjula Basappa, Jacquelyn Willis, Lingshu Wang, Wei Shi, Nicole A. Doria-Rose, Adam S. Olia, Cuiping Liu, Darcy R. Harris, Andrea Carfi, John R. Mascola, Peter D. Kwong, Darin K. Edwards, Hanne Andersen, Mark G. Lewis, Kizzmekia S. Corbett, Martha C. Nason, Adrian B. McDermott, Mehul S. Suthar, Ian N. Moore, Mario Roederer, Nancy J. Sullivan, Daniel C. Douek, Robert A. Seder
doi: https://doi.org/10.1101/2022.02.03.479037
Matthew Gagne
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Juan I. Moliva
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Kathryn E. Foulds
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Shayne F. Andrew
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Barbara J. Flynn
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Anne P. Werner
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Danielle A. Wagner
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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I-Ting Teng
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Bob C. Lin
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Christopher Moore
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Nazaire Jean-Baptiste
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Robin Carroll
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Stephanie L. Foster
2Department of Pediatrics, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, Georgia, 30322, United States of America
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Mit Patel
2Department of Pediatrics, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, Georgia, 30322, United States of America
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Madison Ellis
2Department of Pediatrics, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, Georgia, 30322, United States of America
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Venkata-Viswanadh Edara
2Department of Pediatrics, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, Georgia, 30322, United States of America
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Nahara Vargas Maldonado
2Department of Pediatrics, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, Georgia, 30322, United States of America
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Mahnaz Minai
3Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, 20892, United States of America
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Lauren McCormick
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Christopher Cole Honeycutt
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Bianca M. Nagata
3Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, 20892, United States of America
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Kevin W. Bock
3Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, 20892, United States of America
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Caitlyn N. M. Dulan
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Jamilet Cordon
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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John-Paul M. Todd
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Elizabeth McCarthy
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Laurent Pessaint
4Bioqual, Inc., Rockville, Maryland, 20850, United States of America
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Alex Van Ry
4Bioqual, Inc., Rockville, Maryland, 20850, United States of America
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Brandon Narvaez
4Bioqual, Inc., Rockville, Maryland, 20850, United States of America
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Daniel Valentin
4Bioqual, Inc., Rockville, Maryland, 20850, United States of America
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Anthony Cook
4Bioqual, Inc., Rockville, Maryland, 20850, United States of America
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Alan Dodson
4Bioqual, Inc., Rockville, Maryland, 20850, United States of America
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Katelyn Steingrebe
4Bioqual, Inc., Rockville, Maryland, 20850, United States of America
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Dillon R. Flebbe
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Saule T. Nurmukhambetova
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Sucheta Godbole
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Amy R. Henry
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Farida Laboune
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Jesmine Roberts-Torres
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Cynthia G. Lorang
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Shivani Amin
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Jessica Trost
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Mursal Naisan
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Manjula Basappa
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Jacquelyn Willis
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Lingshu Wang
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Wei Shi
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Nicole A. Doria-Rose
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Adam S. Olia
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Cuiping Liu
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Darcy R. Harris
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Andrea Carfi
5Moderna Inc., Cambridge, MA, 02139, United States of America
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John R. Mascola
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Peter D. Kwong
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Darin K. Edwards
5Moderna Inc., Cambridge, MA, 02139, United States of America
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Hanne Andersen
4Bioqual, Inc., Rockville, Maryland, 20850, United States of America
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Mark G. Lewis
4Bioqual, Inc., Rockville, Maryland, 20850, United States of America
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Kizzmekia S. Corbett
6Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, 02115, United States of America
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Martha C. Nason
7Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Adrian B. McDermott
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Mehul S. Suthar
2Department of Pediatrics, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, Georgia, 30322, United States of America
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Ian N. Moore
8Division of Pathology, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, Georgia, 30329, United States of America
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Mario Roederer
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Nancy J. Sullivan
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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Daniel C. Douek
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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  • For correspondence: ddouek@mail.nih.gov rseder@mail.nih.gov
Robert A. Seder
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, United States of America
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  • For correspondence: ddouek@mail.nih.gov rseder@mail.nih.gov
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Summary

SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to antibody neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-specific vaccines would enhance immunity and protection. Here, nonhuman primates that received mRNA-1273 at weeks 0 and 4 were boosted at week 41 with mRNA-1273 or mRNA-Omicron. Neutralizing antibody titers against D614G were 4760 and 270 reciprocal ID50 at week 6 (peak) and week 41 (pre-boost), respectively, and 320 and 110 for Omicron. Two weeks after boost, titers against D614G and Omicron increased to 5360 and 2980, respectively, for mRNA-1273 and 2670 and 1930 for mRNA-Omicron. Following either boost, 70-80% of spike-specific B cells were cross-reactive against both WA1 and Omicron. Significant and equivalent control of virus replication in lower airways was observed following either boost. Therefore, an Omicron boost may not provide greater immunity or protection compared to a boost with the current mRNA-1273 vaccine.

Competing Interest Statement

K.S.C. is an inventor on U.S. Patent No. 10,960,070 B2 and International Patent Application No. WO/2018/081318 entitled: Prefusion Coronavirus Spike Proteins and Their Use. K.S.C. is an inventor on U.S. Patent Application No. 62/972,886 entitled: 2019-nCoV Vaccine. L.W., W.S., J.R.M., M.R., N.J.S. and D.C.D are inventors on U.S. Patent Application No. 63/147,419 entitled: Antibodies Targeting the Spike Protein of Coronaviruses. L.P., A.V.R., B.N., D.V., A.C., A.D., K.S., H.A. and M.G.L. are employees of Bioqual. K.S.C, L.W. and W.S. are inventors on multiple U.S. Patent Applications entitled Anti-Coronavirus Antibodies and Methods of Use. A.C. and D.K.E. are employees of Moderna. M.S.S. serves on the scientific board of advisors for Moderna and Ocugen. The other authors declare no competing interests.

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mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits comparable B cell expansion, neutralizing antibodies and protection against Omicron
Matthew Gagne, Juan I. Moliva, Kathryn E. Foulds, Shayne F. Andrew, Barbara J. Flynn, Anne P. Werner, Danielle A. Wagner, I-Ting Teng, Bob C. Lin, Christopher Moore, Nazaire Jean-Baptiste, Robin Carroll, Stephanie L. Foster, Mit Patel, Madison Ellis, Venkata-Viswanadh Edara, Nahara Vargas Maldonado, Mahnaz Minai, Lauren McCormick, Christopher Cole Honeycutt, Bianca M. Nagata, Kevin W. Bock, Caitlyn N. M. Dulan, Jamilet Cordon, John-Paul M. Todd, Elizabeth McCarthy, Laurent Pessaint, Alex Van Ry, Brandon Narvaez, Daniel Valentin, Anthony Cook, Alan Dodson, Katelyn Steingrebe, Dillon R. Flebbe, Saule T. Nurmukhambetova, Sucheta Godbole, Amy R. Henry, Farida Laboune, Jesmine Roberts-Torres, Cynthia G. Lorang, Shivani Amin, Jessica Trost, Mursal Naisan, Manjula Basappa, Jacquelyn Willis, Lingshu Wang, Wei Shi, Nicole A. Doria-Rose, Adam S. Olia, Cuiping Liu, Darcy R. Harris, Andrea Carfi, John R. Mascola, Peter D. Kwong, Darin K. Edwards, Hanne Andersen, Mark G. Lewis, Kizzmekia S. Corbett, Martha C. Nason, Adrian B. McDermott, Mehul S. Suthar, Ian N. Moore, Mario Roederer, Nancy J. Sullivan, Daniel C. Douek, Robert A. Seder
bioRxiv 2022.02.03.479037; doi: https://doi.org/10.1101/2022.02.03.479037
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mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits comparable B cell expansion, neutralizing antibodies and protection against Omicron
Matthew Gagne, Juan I. Moliva, Kathryn E. Foulds, Shayne F. Andrew, Barbara J. Flynn, Anne P. Werner, Danielle A. Wagner, I-Ting Teng, Bob C. Lin, Christopher Moore, Nazaire Jean-Baptiste, Robin Carroll, Stephanie L. Foster, Mit Patel, Madison Ellis, Venkata-Viswanadh Edara, Nahara Vargas Maldonado, Mahnaz Minai, Lauren McCormick, Christopher Cole Honeycutt, Bianca M. Nagata, Kevin W. Bock, Caitlyn N. M. Dulan, Jamilet Cordon, John-Paul M. Todd, Elizabeth McCarthy, Laurent Pessaint, Alex Van Ry, Brandon Narvaez, Daniel Valentin, Anthony Cook, Alan Dodson, Katelyn Steingrebe, Dillon R. Flebbe, Saule T. Nurmukhambetova, Sucheta Godbole, Amy R. Henry, Farida Laboune, Jesmine Roberts-Torres, Cynthia G. Lorang, Shivani Amin, Jessica Trost, Mursal Naisan, Manjula Basappa, Jacquelyn Willis, Lingshu Wang, Wei Shi, Nicole A. Doria-Rose, Adam S. Olia, Cuiping Liu, Darcy R. Harris, Andrea Carfi, John R. Mascola, Peter D. Kwong, Darin K. Edwards, Hanne Andersen, Mark G. Lewis, Kizzmekia S. Corbett, Martha C. Nason, Adrian B. McDermott, Mehul S. Suthar, Ian N. Moore, Mario Roederer, Nancy J. Sullivan, Daniel C. Douek, Robert A. Seder
bioRxiv 2022.02.03.479037; doi: https://doi.org/10.1101/2022.02.03.479037

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