mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits similar B cell expansion, neutralizing responses, and protection from Omicron

SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-matched vaccines would enhance protection. Here, nonhuman primates that received mRNA-1273 at weeks 0...

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Published inCell Vol. 185; no. 9; pp. 1556 - 1571.e18
Main Authors Gagne, Matthew, Moliva, Juan I., Foulds, Kathryn E., Andrew, Shayne F., Flynn, Barbara J., Werner, Anne P., Wagner, Danielle A., Teng, I-Ting, Lin, Bob C., Moore, Christopher, Jean-Baptiste, Nazaire, Carroll, Robin, Foster, Stephanie L., Patel, Mit, Ellis, Madison, Edara, Venkata-Viswanadh, Maldonado, Nahara Vargas, Minai, Mahnaz, McCormick, Lauren, Honeycutt, Christopher Cole, Nagata, Bianca M., Bock, Kevin W., Dulan, Caitlyn N.M., Cordon, Jamilet, Flebbe, Dillon R., Todd, John-Paul M., McCarthy, Elizabeth, Pessaint, Laurent, Van Ry, Alex, Narvaez, Brandon, Valentin, Daniel, Cook, Anthony, Dodson, Alan, Steingrebe, Katelyn, Nurmukhambetova, Saule T., Godbole, Sucheta, Henry, Amy R., Laboune, Farida, Roberts-Torres, Jesmine, Lorang, Cynthia G., Amin, Shivani, Trost, Jessica, Naisan, Mursal, Basappa, Manjula, Willis, Jacquelyn, Wang, Lingshu, Shi, Wei, Doria-Rose, Nicole A., Zhang, Yi, Yang, Eun Sung, Leung, Kwanyee, O’Dell, Sijy, Schmidt, Stephen D., Olia, Adam S., Liu, Cuiping, Harris, Darcy R., Chuang, Gwo-Yu, Stewart-Jones, Guillaume, Renzi, Isabella, Lai, Yen-Ting, Malinowski, Agata, Wu, Kai, Mascola, John R., Carfi, Andrea, Kwong, Peter D., Edwards, Darin K., Lewis, Mark G., Andersen, Hanne, Corbett, Kizzmekia S., Nason, Martha C., McDermott, Adrian B., Suthar, Mehul S., Moore, Ian N., Roederer, Mario, Sullivan, Nancy J., Douek, Daniel C., Seder, Robert A.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 28.04.2022
Cell Press
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Abstract SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-matched vaccines would enhance 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 titers against D614G were 4,760 and 270 reciprocal ID50 at week 6 (peak) and week 41 (preboost), respectively, and 320 and 110 for Omicron. 2 weeks after the boost, titers against D614G and Omicron increased to 5,360 and 2,980 for mRNA-1273 boost and 2,670 and 1,930 for mRNA-Omicron, respectively. Similar increases against BA.2 were observed. Following either boost, 70%–80% of spike-specific B cells were cross-reactive against WA1 and Omicron. Equivalent control of virus replication in lower airways was observed following Omicron challenge 1 month after either boost. These data show that mRNA-1273 and mRNA-Omicron elicit comparable immunity and protection shortly after the boost. [Display omitted] •mRNA-1273 prime induces cross-reactive B cells to Omicron and ancestral strains•Boosting with mRNA-1273 or mRNA-Omicron enhances neutralization of Omicron•Either boost expands B cells cross-reactive to Omicron and ancestral strains•mRNA-1273 or mRNA-Omicron boost is protective against Omicron replication in the lungs Boosting previously vaccinated nonhuman primates with either the mRNA-1273 or mRNA-Omicron vaccine expands cross-reactive memory B cells and elicits similar levels of protection upon challenge with SARS-CoV-2 Omicron.
AbstractList SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-matched vaccines would enhance 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 titers against D614G were 4,760 and 270 reciprocal ID 50 at week 6 (peak) and week 41 (preboost), respectively, and 320 and 110 for Omicron. 2 weeks after the boost, titers against D614G and Omicron increased to 5,360 and 2,980 for mRNA-1273 boost and 2,670 and 1,930 for mRNA-Omicron, respectively. Similar increases against BA.2 were observed. Following either boost, 70%–80% of spike-specific B cells were cross-reactive against WA1 and Omicron. Equivalent control of virus replication in lower airways was observed following Omicron challenge 1 month after either boost. These data show that mRNA-1273 and mRNA-Omicron elicit comparable immunity and protection shortly after the boost. Boosting previously vaccinated nonhuman primates with either the mRNA-1273 or mRNA-Omicron vaccine expands cross-reactive memory B cells and elicits similar levels of protection upon challenge with SARS-CoV-2 Omicron.
SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-matched vaccines would enhance 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 titers against D614G were 4,760 and 270 reciprocal ID at week 6 (peak) and week 41 (preboost), respectively, and 320 and 110 for Omicron. 2 weeks after the boost, titers against D614G and Omicron increased to 5,360 and 2,980 for mRNA-1273 boost and 2,670 and 1,930 for mRNA-Omicron, respectively. Similar increases against BA.2 were observed. Following either boost, 70%-80% of spike-specific B cells were cross-reactive against WA1 and Omicron. Equivalent control of virus replication in lower airways was observed following Omicron challenge 1 month after either boost. These data show that mRNA-1273 and mRNA-Omicron elicit comparable immunity and protection shortly after the boost.
SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-matched vaccines would enhance 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 titers against D614G were 4,760 and 270 reciprocal ID50 at week 6 (peak) and week 41 (preboost), respectively, and 320 and 110 for Omicron. 2 weeks after the boost, titers against D614G and Omicron increased to 5,360 and 2,980 for mRNA-1273 boost and 2,670 and 1,930 for mRNA-Omicron, respectively. Similar increases against BA.2 were observed. Following either boost, 70%–80% of spike-specific B cells were cross-reactive against WA1 and Omicron. Equivalent control of virus replication in lower airways was observed following Omicron challenge 1 month after either boost. These data show that mRNA-1273 and mRNA-Omicron elicit comparable immunity and protection shortly after the boost. [Display omitted] •mRNA-1273 prime induces cross-reactive B cells to Omicron and ancestral strains•Boosting with mRNA-1273 or mRNA-Omicron enhances neutralization of Omicron•Either boost expands B cells cross-reactive to Omicron and ancestral strains•mRNA-1273 or mRNA-Omicron boost is protective against Omicron replication in the lungs Boosting previously vaccinated nonhuman primates with either the mRNA-1273 or mRNA-Omicron vaccine expands cross-reactive memory B cells and elicits similar levels of protection upon challenge with SARS-CoV-2 Omicron.
SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-matched vaccines would enhance 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 titers against D614G were 4,760 and 270 reciprocal ID₅₀ at week 6 (peak) and week 41 (preboost), respectively, and 320 and 110 for Omicron. 2 weeks after the boost, titers against D614G and Omicron increased to 5,360 and 2,980 for mRNA-1273 boost and 2,670 and 1,930 for mRNA-Omicron, respectively. Similar increases against BA.2 were observed. Following either boost, 70%–80% of spike-specific B cells were cross-reactive against WA1 and Omicron. Equivalent control of virus replication in lower airways was observed following Omicron challenge 1 month after either boost. These data show that mRNA-1273 and mRNA-Omicron elicit comparable immunity and protection shortly after the boost.
SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-matched vaccines would enhance 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 titers against D614G were 4,760 and 270 reciprocal ID50 at week 6 (peak) and week 41 (preboost), respectively, and 320 and 110 for Omicron. 2 weeks after the boost, titers against D614G and Omicron increased to 5,360 and 2,980 for mRNA-1273 boost and 2,670 and 1,930 for mRNA-Omicron, respectively. Similar increases against BA.2 were observed. Following either boost, 70%-80% of spike-specific B cells were cross-reactive against WA1 and Omicron. Equivalent control of virus replication in lower airways was observed following Omicron challenge 1 month after either boost. These data show that mRNA-1273 and mRNA-Omicron elicit comparable immunity and protection shortly after the boost.SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-matched vaccines would enhance 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 titers against D614G were 4,760 and 270 reciprocal ID50 at week 6 (peak) and week 41 (preboost), respectively, and 320 and 110 for Omicron. 2 weeks after the boost, titers against D614G and Omicron increased to 5,360 and 2,980 for mRNA-1273 boost and 2,670 and 1,930 for mRNA-Omicron, respectively. Similar increases against BA.2 were observed. Following either boost, 70%-80% of spike-specific B cells were cross-reactive against WA1 and Omicron. Equivalent control of virus replication in lower airways was observed following Omicron challenge 1 month after either boost. These data show that mRNA-1273 and mRNA-Omicron elicit comparable immunity and protection shortly after the boost.
Author Douek, Daniel C.
Shi, Wei
Corbett, Kizzmekia S.
Godbole, Sucheta
Todd, John-Paul M.
Henry, Amy R.
Lai, Yen-Ting
Naisan, Mursal
Bock, Kevin W.
Stewart-Jones, Guillaume
Dodson, Alan
Carfi, Andrea
Flebbe, Dillon R.
Van Ry, Alex
Roederer, Mario
McCormick, Lauren
Minai, Mahnaz
Wagner, Danielle A.
Ellis, Madison
McDermott, Adrian B.
Patel, Mit
Dulan, Caitlyn N.M.
McCarthy, Elizabeth
Foster, Stephanie L.
O’Dell, Sijy
Harris, Darcy R.
Foulds, Kathryn E.
Laboune, Farida
Edara, Venkata-Viswanadh
Steingrebe, Katelyn
Cordon, Jamilet
Cook, Anthony
Olia, Adam S.
Lewis, Mark G.
Chuang, Gwo-Yu
Werner, Anne P.
Willis, Jacquelyn
Nurmukhambetova, Saule T.
Amin, Shivani
Lorang, Cynthia G.
Yang, Eun Sung
Suthar, Mehul S.
Trost, Jessica
Malinowski, Agata
Zhang, Yi
Lin, Bob C.
Narvaez, Brandon
Kwong, Peter D.
Valentin, Daniel
Renzi, Isabella
Roberts-Torres, Jesmine
Pessaint, Laurent
Edwards, Darin K.
Maldonado, Nahara Vargas
Seder, Robert A.
Teng, I-Ting
Schmidt, Stephen D.
Sullivan, Nancy J.
Moliva, Juan I.
Wu, Kai
Flynn, Barbara J.
Andrew, Shayne F.
Wang, Lingshu
Gagn
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  givenname: Peter D.
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  organization: Moderna Inc., Cambridge, MA 02139, USA
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  surname: Nason
  fullname: Nason, Martha C.
  organization: Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
– sequence: 71
  givenname: Adrian B.
  surname: McDermott
  fullname: McDermott, Adrian B.
  organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
– sequence: 72
  givenname: Mehul S.
  surname: Suthar
  fullname: Suthar, Mehul S.
  organization: Department of Pediatrics, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, GA 30322, USA
– sequence: 73
  givenname: Ian N.
  surname: Moore
  fullname: Moore, Ian N.
  organization: Division of Pathology, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, GA 30329, USA
– sequence: 74
  givenname: Mario
  surname: Roederer
  fullname: Roederer, Mario
  organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
– sequence: 75
  givenname: Nancy J.
  surname: Sullivan
  fullname: Sullivan, Nancy J.
  organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
– sequence: 76
  givenname: Daniel C.
  surname: Douek
  fullname: Douek, Daniel C.
  email: ddouek@mail.nih.gov
  organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
– sequence: 77
  givenname: Robert A.
  orcidid: 0000-0003-3133-0849
  surname: Seder
  fullname: Seder, Robert A.
  email: rseder@mail.nih.gov
  organization: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
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Keywords COVID-19
original antigenic sin
SARS-CoV-2
antibody
immune memory
boost
Omicron
B cells
T cells
mRNA vaccine
Language English
License Published by Elsevier Inc.
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
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Snippet SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to neutralization following immunization with ancestral spike-matched vaccines. It is...
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StartPage 1556
SubjectTerms 2019-nCoV Vaccine mRNA-1273
Animals
Antibodies, Neutralizing
Antibodies, Viral
antibody
B cells
B-lymphocytes
boost
COVID-19
COVID-19 - prevention & control
immune memory
immunity
immunization
Macaca
mRNA vaccine
neutralization
Omicron
original antigenic sin
RNA, Messenger
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
T cells
virus replication
Title mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits similar B cell expansion, neutralizing responses, and protection from Omicron
URI https://dx.doi.org/10.1016/j.cell.2022.03.038
https://www.ncbi.nlm.nih.gov/pubmed/35447072
https://www.proquest.com/docview/2654294148
https://www.proquest.com/docview/2660983992
https://pubmed.ncbi.nlm.nih.gov/PMC8947944
Volume 185
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