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Vaccination with SARS-CoV-2 Spike Protein and AS03 Adjuvant Induces Rapid Anamnestic Antibodies in the Lung and Protects Against Virus Challenge in Nonhuman Primates

Abstract Adjuvanted soluble protein vaccines have been used extensively in humans for protection against various viral infections based on their robust induction of antibody responses. Here, soluble prefusion-stabilized spike trimers (preS dTM) from the severe acute respiratory syndrome coronavirus...

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Published in:bioRxiv 2021-03
Main Authors: Francica, Joseph R, Flynn, Barbara J, Foulds, Kathryn E, Noe, Amy T, Werner, Anne P, Moore, Ian N, Gagne, Matthew, Johnston, Timothy S, Tucker, Courtney, Davis, Rachel L, Flach, Britta, Sarah O’connell, Andrew, Shayne F, Lamb, Evan, Flebbe, Dillon R, Nurmukhambetova, Saule T, Donaldson, Mitzi M, Todd, John-Paul M, Alex Lee Zhu, Atyeo, Caroline, Fischinger, Stephanie, Gorman, Matthew J, Shin, Sally, Edara, Venkata Viswanadh, Floyd, Katharine, Lai, Lilin, Tylor, Alida, Mccarthy, Elizabeth, Lecouturier, Valerie, Ruiz, Sophie, Berry, Catherine, Tibbitts, Timothy, Andersen, Hanne, Cook, Anthony, Dodson, Alan, Pessaint, Laurent, Alex Van Ry, Koutsoukos, Marguerite, Gutzeit, Cindy, I-Ting, Teng, Zhou, Tongqing, Li, Dapeng, Haynes, Barton F, Kwong, Peter D, Mcdermott, Adrian, Lewis, Mark G, Fu, Tong Ming, Chicz, Roman, Van Der Most, Robbert, Corbett, Kizzmekia S, Suthar, Mehul S, Alter, Galit, Roederer, Mario, Sullivan, Nancy J, Douek, Daniel C, Graham, Barney S, Casimiro, Danilo, Seder, Robert A
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container_title bioRxiv
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creator Francica, Joseph R
Flynn, Barbara J
Foulds, Kathryn E
Noe, Amy T
Werner, Anne P
Moore, Ian N
Gagne, Matthew
Johnston, Timothy S
Tucker, Courtney
Davis, Rachel L
Flach, Britta
Sarah O’connell
Andrew, Shayne F
Lamb, Evan
Flebbe, Dillon R
Nurmukhambetova, Saule T
Donaldson, Mitzi M
Todd, John-Paul M
Alex Lee Zhu
Atyeo, Caroline
Fischinger, Stephanie
Gorman, Matthew J
Shin, Sally
Edara, Venkata Viswanadh
Floyd, Katharine
Lai, Lilin
Tylor, Alida
Mccarthy, Elizabeth
Lecouturier, Valerie
Ruiz, Sophie
Berry, Catherine
Tibbitts, Timothy
Andersen, Hanne
Cook, Anthony
Dodson, Alan
Pessaint, Laurent
Alex Van Ry
Koutsoukos, Marguerite
Gutzeit, Cindy
I-Ting, Teng
Zhou, Tongqing
Li, Dapeng
Haynes, Barton F
Kwong, Peter D
Mcdermott, Adrian
Lewis, Mark G
Fu, Tong Ming
Chicz, Roman
Van Der Most, Robbert
Corbett, Kizzmekia S
Suthar, Mehul S
Alter, Galit
Roederer, Mario
Sullivan, Nancy J
Douek, Daniel C
Graham, Barney S
Casimiro, Danilo
Seder, Robert A
description Abstract Adjuvanted soluble protein vaccines have been used extensively in humans for protection against various viral infections based on their robust induction of antibody responses. Here, soluble prefusion-stabilized spike trimers (preS dTM) from the severe acute respiratory syndrome coronavirus (SARS-CoV-2) were formulated with the adjuvant AS03 and administered twice to nonhuman primates (NHP). Binding and functional neutralization assays and systems serology revealed that NHP developed AS03-dependent multi-functional humoral responses that targeted multiple spike domains and bound to a variety of antibody FC receptors mediating effector functions in vitro. Pseudovirus and live virus neutralizing IC50 titers were on average greater than 1000 and significantly higher than a panel of human convalescent sera. NHP were challenged intranasally and intratracheally with a high dose (3×106 PFU) of SARS-CoV-2 (USA-WA1/2020 isolate). Two days post-challenge, vaccinated NHP showed rapid control of viral replication in both the upper and lower airways. Notably, vaccinated NHP also had increased spike-specific IgG antibody responses in the lung as early as 2 days post challenge. Moreover, vaccine-induced IgG mediated protection from SARS-CoV-2 challenge following passive transfer to hamsters. These data show that antibodies induced by the AS03-adjuvanted preS dTM vaccine are sufficient to mediate protection against SARS-CoV-2 and support the evaluation of this vaccine in human clinical trials. Competing Interest Statement All authors have declared the following interests: VL, TB, CB, SR, TMF, DC, RC are Sanofi Pasteur employees and may hold stock. MK, RvdM, and CG are employees of the GSK group of companies and report ownership of GSK shares.
doi_str_mv 10.1101/2021.03.02.433390
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Collection</collection><collection>ProQuest One Community College</collection><collection>Coronavirus Research Database</collection><collection>ProQuest Central</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>ProQuest Biological Science Journals</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>bioRxiv</collection></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Francica, Joseph R</au><au>Flynn, Barbara J</au><au>Foulds, Kathryn E</au><au>Noe, Amy T</au><au>Werner, Anne P</au><au>Moore, Ian N</au><au>Gagne, Matthew</au><au>Johnston, Timothy S</au><au>Tucker, Courtney</au><au>Davis, Rachel L</au><au>Flach, Britta</au><au>Sarah O’connell</au><au>Andrew, Shayne F</au><au>Lamb, Evan</au><au>Flebbe, Dillon R</au><au>Nurmukhambetova, Saule T</au><au>Donaldson, Mitzi M</au><au>Todd, John-Paul M</au><au>Alex Lee Zhu</au><au>Atyeo, Caroline</au><au>Fischinger, Stephanie</au><au>Gorman, Matthew J</au><au>Shin, Sally</au><au>Edara, Venkata Viswanadh</au><au>Floyd, Katharine</au><au>Lai, Lilin</au><au>Tylor, Alida</au><au>Mccarthy, Elizabeth</au><au>Lecouturier, Valerie</au><au>Ruiz, Sophie</au><au>Berry, Catherine</au><au>Tibbitts, Timothy</au><au>Andersen, Hanne</au><au>Cook, Anthony</au><au>Dodson, Alan</au><au>Pessaint, Laurent</au><au>Alex Van Ry</au><au>Koutsoukos, Marguerite</au><au>Gutzeit, Cindy</au><au>I-Ting, Teng</au><au>Zhou, Tongqing</au><au>Li, Dapeng</au><au>Haynes, Barton F</au><au>Kwong, Peter D</au><au>Mcdermott, Adrian</au><au>Lewis, Mark G</au><au>Fu, Tong Ming</au><au>Chicz, Roman</au><au>Van Der Most, Robbert</au><au>Corbett, Kizzmekia S</au><au>Suthar, Mehul S</au><au>Alter, Galit</au><au>Roederer, Mario</au><au>Sullivan, Nancy J</au><au>Douek, Daniel C</au><au>Graham, Barney S</au><au>Casimiro, Danilo</au><au>Seder, Robert A</au><format>book</format><genre>document</genre><ristype>GEN</ristype><atitle>Vaccination with SARS-CoV-2 Spike Protein and AS03 Adjuvant Induces Rapid Anamnestic Antibodies in the Lung and Protects Against Virus Challenge in Nonhuman Primates</atitle><jtitle>bioRxiv</jtitle><date>2021-03-02</date><risdate>2021</risdate><eissn>2692-8205</eissn><abstract>Abstract Adjuvanted soluble protein vaccines have been used extensively in humans for protection against various viral infections based on their robust induction of antibody responses. Here, soluble prefusion-stabilized spike trimers (preS dTM) from the severe acute respiratory syndrome coronavirus (SARS-CoV-2) were formulated with the adjuvant AS03 and administered twice to nonhuman primates (NHP). Binding and functional neutralization assays and systems serology revealed that NHP developed AS03-dependent multi-functional humoral responses that targeted multiple spike domains and bound to a variety of antibody FC receptors mediating effector functions in vitro. Pseudovirus and live virus neutralizing IC50 titers were on average greater than 1000 and significantly higher than a panel of human convalescent sera. NHP were challenged intranasally and intratracheally with a high dose (3×106 PFU) of SARS-CoV-2 (USA-WA1/2020 isolate). Two days post-challenge, vaccinated NHP showed rapid control of viral replication in both the upper and lower airways. Notably, vaccinated NHP also had increased spike-specific IgG antibody responses in the lung as early as 2 days post challenge. Moreover, vaccine-induced IgG mediated protection from SARS-CoV-2 challenge following passive transfer to hamsters. These data show that antibodies induced by the AS03-adjuvanted preS dTM vaccine are sufficient to mediate protection against SARS-CoV-2 and support the evaluation of this vaccine in human clinical trials. Competing Interest Statement All authors have declared the following interests: VL, TB, CB, SR, TMF, DC, RC are Sanofi Pasteur employees and may hold stock. MK, RvdM, and CG are employees of the GSK group of companies and report ownership of GSK shares.</abstract><cop>Cold Spring Harbor</cop><pub>Cold Spring Harbor Laboratory Press</pub><doi>10.1101/2021.03.02.433390</doi><tpages>42</tpages><edition>1.1</edition><oa>free_for_read</oa></addata></record>
fulltext fulltext_linktorsrc
identifier EISSN: 2692-8205
ispartof bioRxiv, 2021-03
issn 2692-8205
language eng
recordid cdi_proquest_journals_2505151434
source Coronavirus Research Database
subjects Antibodies
Clinical trials
Coronaviruses
Fc receptors
Immunoglobulin G
Immunology
Serology
Severe acute respiratory syndrome coronavirus 2
Spike protein
Trimers
Vaccines
Viral infections
title Vaccination with SARS-CoV-2 Spike Protein and AS03 Adjuvant Induces Rapid Anamnestic Antibodies in the Lung and Protects Against Virus Challenge in Nonhuman Primates
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