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Unglycosylated Soluble SARS-CoV-2 Receptor Binding Domain (RBD) Produced in E. coli Combined with the Army Liposomal Formulation Containing QS21 (ALFQ) Elicits Neutralizing Antibodies against Mismatched Variants

The emergence of novel potentially pandemic pathogens necessitates the rapid manufacture and deployment of effective, stable, and locally manufacturable vaccines on a global scale. In this study, the ability of the Escherichia coli expression system to produce the receptor binding domain (RBD) of th...

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Autores principales: Balasubramaniyam, Arasu, Ryan, Emma, Brown, Dallas, Hamza, Therwa, Harrison, William, Gan, Michael, Sankhala, Rajeshwer S., Chen, Wei-Hung, Martinez, Elizabeth J., Jensen, Jaime L., Dussupt, Vincent, Mendez-Rivera, Letzibeth, Mayer, Sandra, King, Jocelyn, Michael, Nelson L., Regules, Jason, Krebs, Shelly, Rao, Mangala, Matyas, Gary R., Joyce, M. Gordon, Batchelor, Adrian H., Gromowski, Gregory D., Dutta, Sheetij
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9864931/
https://www.ncbi.nlm.nih.gov/pubmed/36679887
http://dx.doi.org/10.3390/vaccines11010042
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author Balasubramaniyam, Arasu
Ryan, Emma
Brown, Dallas
Hamza, Therwa
Harrison, William
Gan, Michael
Sankhala, Rajeshwer S.
Chen, Wei-Hung
Martinez, Elizabeth J.
Jensen, Jaime L.
Dussupt, Vincent
Mendez-Rivera, Letzibeth
Mayer, Sandra
King, Jocelyn
Michael, Nelson L.
Regules, Jason
Krebs, Shelly
Rao, Mangala
Matyas, Gary R.
Joyce, M. Gordon
Batchelor, Adrian H.
Gromowski, Gregory D.
Dutta, Sheetij
author_facet Balasubramaniyam, Arasu
Ryan, Emma
Brown, Dallas
Hamza, Therwa
Harrison, William
Gan, Michael
Sankhala, Rajeshwer S.
Chen, Wei-Hung
Martinez, Elizabeth J.
Jensen, Jaime L.
Dussupt, Vincent
Mendez-Rivera, Letzibeth
Mayer, Sandra
King, Jocelyn
Michael, Nelson L.
Regules, Jason
Krebs, Shelly
Rao, Mangala
Matyas, Gary R.
Joyce, M. Gordon
Batchelor, Adrian H.
Gromowski, Gregory D.
Dutta, Sheetij
author_sort Balasubramaniyam, Arasu
collection PubMed
description The emergence of novel potentially pandemic pathogens necessitates the rapid manufacture and deployment of effective, stable, and locally manufacturable vaccines on a global scale. In this study, the ability of the Escherichia coli expression system to produce the receptor binding domain (RBD) of the SARS-CoV-2 spike protein was evaluated. The RBD of the original Wuhan-Hu1 variant and of the Alpha and Beta variants of concern (VoC) were expressed in E. coli, and their biochemical and immunological profiles were compared to RBD produced in mammalian cells. The E. coli-produced RBD variants recapitulated the structural character of mammalian-expressed RBD and bound to human angiotensin converting enzyme (ACE2) receptor and a panel of neutralizing SARS-CoV-2 monoclonal antibodies. A pilot vaccination in mice with bacterial RBDs formulated with a novel liposomal adjuvant, Army Liposomal Formulation containing QS21 (ALFQ), induced polyclonal antibodies that inhibited RBD association to ACE2 in vitro and potently neutralized homologous and heterologous SARS-CoV-2 pseudoviruses. Although all vaccines induced neutralization of the non-vaccine Delta variant, only the Beta RBD vaccine produced in E. coli and mammalian cells effectively neutralized the Omicron BA.1 pseudovirus. These outcomes warrant further exploration of E. coli as an expression platform for non-glycosylated, soluble immunogens for future rapid response to emerging pandemic pathogens.
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spelling pubmed-98649312023-01-22 Unglycosylated Soluble SARS-CoV-2 Receptor Binding Domain (RBD) Produced in E. coli Combined with the Army Liposomal Formulation Containing QS21 (ALFQ) Elicits Neutralizing Antibodies against Mismatched Variants Balasubramaniyam, Arasu Ryan, Emma Brown, Dallas Hamza, Therwa Harrison, William Gan, Michael Sankhala, Rajeshwer S. Chen, Wei-Hung Martinez, Elizabeth J. Jensen, Jaime L. Dussupt, Vincent Mendez-Rivera, Letzibeth Mayer, Sandra King, Jocelyn Michael, Nelson L. Regules, Jason Krebs, Shelly Rao, Mangala Matyas, Gary R. Joyce, M. Gordon Batchelor, Adrian H. Gromowski, Gregory D. Dutta, Sheetij Vaccines (Basel) Article The emergence of novel potentially pandemic pathogens necessitates the rapid manufacture and deployment of effective, stable, and locally manufacturable vaccines on a global scale. In this study, the ability of the Escherichia coli expression system to produce the receptor binding domain (RBD) of the SARS-CoV-2 spike protein was evaluated. The RBD of the original Wuhan-Hu1 variant and of the Alpha and Beta variants of concern (VoC) were expressed in E. coli, and their biochemical and immunological profiles were compared to RBD produced in mammalian cells. The E. coli-produced RBD variants recapitulated the structural character of mammalian-expressed RBD and bound to human angiotensin converting enzyme (ACE2) receptor and a panel of neutralizing SARS-CoV-2 monoclonal antibodies. A pilot vaccination in mice with bacterial RBDs formulated with a novel liposomal adjuvant, Army Liposomal Formulation containing QS21 (ALFQ), induced polyclonal antibodies that inhibited RBD association to ACE2 in vitro and potently neutralized homologous and heterologous SARS-CoV-2 pseudoviruses. Although all vaccines induced neutralization of the non-vaccine Delta variant, only the Beta RBD vaccine produced in E. coli and mammalian cells effectively neutralized the Omicron BA.1 pseudovirus. These outcomes warrant further exploration of E. coli as an expression platform for non-glycosylated, soluble immunogens for future rapid response to emerging pandemic pathogens. MDPI 2022-12-25 /pmc/articles/PMC9864931/ /pubmed/36679887 http://dx.doi.org/10.3390/vaccines11010042 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Balasubramaniyam, Arasu
Ryan, Emma
Brown, Dallas
Hamza, Therwa
Harrison, William
Gan, Michael
Sankhala, Rajeshwer S.
Chen, Wei-Hung
Martinez, Elizabeth J.
Jensen, Jaime L.
Dussupt, Vincent
Mendez-Rivera, Letzibeth
Mayer, Sandra
King, Jocelyn
Michael, Nelson L.
Regules, Jason
Krebs, Shelly
Rao, Mangala
Matyas, Gary R.
Joyce, M. Gordon
Batchelor, Adrian H.
Gromowski, Gregory D.
Dutta, Sheetij
Unglycosylated Soluble SARS-CoV-2 Receptor Binding Domain (RBD) Produced in E. coli Combined with the Army Liposomal Formulation Containing QS21 (ALFQ) Elicits Neutralizing Antibodies against Mismatched Variants
title Unglycosylated Soluble SARS-CoV-2 Receptor Binding Domain (RBD) Produced in E. coli Combined with the Army Liposomal Formulation Containing QS21 (ALFQ) Elicits Neutralizing Antibodies against Mismatched Variants
title_full Unglycosylated Soluble SARS-CoV-2 Receptor Binding Domain (RBD) Produced in E. coli Combined with the Army Liposomal Formulation Containing QS21 (ALFQ) Elicits Neutralizing Antibodies against Mismatched Variants
title_fullStr Unglycosylated Soluble SARS-CoV-2 Receptor Binding Domain (RBD) Produced in E. coli Combined with the Army Liposomal Formulation Containing QS21 (ALFQ) Elicits Neutralizing Antibodies against Mismatched Variants
title_full_unstemmed Unglycosylated Soluble SARS-CoV-2 Receptor Binding Domain (RBD) Produced in E. coli Combined with the Army Liposomal Formulation Containing QS21 (ALFQ) Elicits Neutralizing Antibodies against Mismatched Variants
title_short Unglycosylated Soluble SARS-CoV-2 Receptor Binding Domain (RBD) Produced in E. coli Combined with the Army Liposomal Formulation Containing QS21 (ALFQ) Elicits Neutralizing Antibodies against Mismatched Variants
title_sort unglycosylated soluble sars-cov-2 receptor binding domain (rbd) produced in e. coli combined with the army liposomal formulation containing qs21 (alfq) elicits neutralizing antibodies against mismatched variants
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9864931/
https://www.ncbi.nlm.nih.gov/pubmed/36679887
http://dx.doi.org/10.3390/vaccines11010042
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