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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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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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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. 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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. 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Ming</creatorcontrib><creatorcontrib>Chicz, Roman</creatorcontrib><creatorcontrib>Van Der Most, Robbert</creatorcontrib><creatorcontrib>Corbett, Kizzmekia S</creatorcontrib><creatorcontrib>Suthar, Mehul S</creatorcontrib><creatorcontrib>Alter, Galit</creatorcontrib><creatorcontrib>Roederer, Mario</creatorcontrib><creatorcontrib>Sullivan, Nancy J</creatorcontrib><creatorcontrib>Douek, Daniel C</creatorcontrib><creatorcontrib>Graham, Barney S</creatorcontrib><creatorcontrib>Casimiro, Danilo</creatorcontrib><creatorcontrib>Seder, Robert A</creatorcontrib><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science 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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