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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.
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.
  • Balasubramaniyam A; Biologics Research and Development Branch, Structural Vaccinology Laboratory, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Ryan E; Biologics Research and Development Branch, Structural Vaccinology Laboratory, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Brown D; Biologics Research and Development Branch, Structural Vaccinology Laboratory, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Hamza T; Biologics Research and Development Branch, Structural Vaccinology Laboratory, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Harrison W; Biologics Research and Development Branch, Structural Vaccinology Laboratory, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Gan M; Biologics Research and Development Branch, Structural Vaccinology Laboratory, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Sankhala RS; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Chen WH; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA.
  • Martinez EJ; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Jensen JL; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA.
  • Dussupt V; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Mendez-Rivera L; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA.
  • Mayer S; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • King J; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA.
  • Michael NL; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Regules J; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA.
  • Krebs S; U.S. Military HIV Research Program, B-cell Biology Laboratory, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Rao M; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Matyas GR; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA.
  • Joyce MG; U.S. Military HIV Research Program, B-cell Biology Laboratory, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Batchelor AH; Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Gromowski GD; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA.
  • Dutta S; Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Vaccines (Basel) ; 11(1)2022 Dec 25.
Article in English | MEDLINE | ID: covidwho-2227865
ABSTRACT
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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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies Topics: Vaccines / Variants Language: English Year: 2022 Document Type: Article Affiliation country: Vaccines11010042

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies Topics: Vaccines / Variants Language: English Year: 2022 Document Type: Article Affiliation country: Vaccines11010042