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

Arasu Balasubramaniyam; Emma Ryan; Dallas Brown; Therwa Hamza; William Harrison; Michael Gan; Rajeshwer S. Sankhala; Wei-Hung Chen; Elizabeth J. Martinez; Jaime L. Jensen; Vincent Dussupt; Letzibeth Mendez-Rivera; Sandra Mayer; Jocelyn King; Nelson L. Michael; Jason Regules; Shelly Krebs; Mangala Rao; Gary R. Matyas; M. Gordon Joyce; Adrian H. Batchelor; Gregory D. Gromowski; Sheetij Dutta

doi:10.3390/vaccines11010042

Vaccines (Dec 2022)

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

Arasu Balasubramaniyam,
Emma Ryan,
Dallas Brown,
Therwa Hamza,
William Harrison,
Michael Gan,
Rajeshwer S. Sankhala,
Wei-Hung Chen,
Elizabeth J. Martinez,
Jaime L. Jensen,
Vincent Dussupt,
Letzibeth Mendez-Rivera,
Sandra Mayer,
Jocelyn King,
Nelson L. Michael,
Jason Regules,
Shelly Krebs,
Mangala Rao,
Gary R. Matyas,
M. Gordon Joyce,
Adrian H. Batchelor,
Gregory D. Gromowski,
Sheetij Dutta

Affiliations

Arasu Balasubramaniyam: Biologics Research and Development Branch, Structural Vaccinology Laboratory, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Emma Ryan: Biologics Research and Development Branch, Structural Vaccinology Laboratory, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Dallas Brown: Biologics Research and Development Branch, Structural Vaccinology Laboratory, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Therwa Hamza: Biologics Research and Development Branch, Structural Vaccinology Laboratory, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
William Harrison: Biologics Research and Development Branch, Structural Vaccinology Laboratory, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Michael Gan: Biologics Research and Development Branch, Structural Vaccinology Laboratory, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Rajeshwer S. Sankhala: Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Wei-Hung Chen: Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Elizabeth J. Martinez: Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Jaime L. Jensen: Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Vincent Dussupt: Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Letzibeth Mendez-Rivera: Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Sandra Mayer: Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Jocelyn King: Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Nelson L. Michael: Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Jason Regules: Biologics Research and Development Branch, Structural Vaccinology Laboratory, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Shelly Krebs: Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Mangala Rao: U.S. Military HIV Research Program, Laboratory of Adjuvant and Antigen Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Gary R. Matyas: U.S. Military HIV Research Program, Laboratory of Adjuvant and Antigen Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
M. Gordon Joyce: Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Adrian H. Batchelor: Biologics Research and Development Branch, Structural Vaccinology Laboratory, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Gregory D. Gromowski: Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
Sheetij Dutta: Biologics Research and Development Branch, Structural Vaccinology Laboratory, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA

DOI: https://doi.org/10.3390/vaccines11010042
Journal volume & issue: Vol. 11, no. 1
p. 42

Abstract

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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.

Published in Vaccines

ISSN: 2076-393X (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine
Website: http://www.mdpi.com/journal/vaccines

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