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Effects of aluminum-salt, CpG and emulsion adjuvants on the stability and immunogenicity of a virus-like particle displaying the SARS-CoV-2 receptor-binding domain (RBD)

Human Vaccines and Immunotherapeutics, ISSN: 2164-554X, Vol: 19, Issue: 2, Page: 2264594
2023
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  • Captures
    6
  • Mentions
    1
    • News Mentions
      1
      • 1

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Research from University of Kansas Provide New Insights into COVID-19 [Effects of aluminum-salt, CpG and emulsion adjuvants on the stability and immunogenicity of a virus-like particle displaying the SARS-CoV-2 receptor-binding domain (RBD)]

2023 NOV 22 (NewsRx) -- By a News Reporter-Staff News Editor at NewsRx COVID-19 Daily -- Research findings on COVID-19 are discussed in a new

Article Description

Second-generation COVID-19 vaccines with improved immunogenicity (e.g., breadth, duration) and availability (e.g., lower costs, refrigerator stable) are needed to enhance global coverage. In this work, we formulated a clinical-stage SARS-CoV-2 receptor-binding domain (RBD) virus-like particle (VLP) vaccine candidate (IVX-411) with widely available adjuvants. Specifically, we assessed the in vitro storage stability and in vivo mouse immunogenicity of IVX-411 formulated with aluminum-salt adjuvants (Alhydrogel™, AH and Adjuphos™, AP), without or with the TLR-9 agonist CpG-1018™ (CpG), and compared these profiles to IVX-411 adjuvanted with an oil-in-water nano-emulsion (AddaVax™, AV). Although IVX-411 bound both AH and AP, lower binding strength of antigen to AP was observed by Langmuir binding isotherms. Interestingly, AH- and AP-adsorbed IVX-411 had similar storage stability profiles as measured by antigen-binding assays (competitive ELISAs), but the latter displayed higher pseudovirus neutralizing titers (pNT) in mice, at levels comparable to titers elicited by AV-adjuvanted IVX-411. CpG addition to alum (AP or AH) resulted in a marginal trend of improved pNTs in stressed samples only, yet did not impact the storage stability profiles of IVX-411. In contrast, previous work with AH-formulations of a monomeric RBD antigen showed greatly improved immunogenicity and decreased stability upon CpG addition to alum. At elevated temperatures (25, 37°C), IVX-411 formulated with AH or AP displayed decreased in vitro stability compared to AV-formulated IVX-411and this rank-ordering correlated with in vivo performance (mouse pNT values). This case study highlights the importance of characterizing antigen-adjuvant interactions to develop low cost, aluminum-salt adjuvanted recombinant subunit vaccine candidates.

Bibliographic Details

Kumru, Ozan S; Bajoria, Sakshi; Kaur, Kawaljit; Hickey, John M; Van Slyke, Greta; Doering, Jennifer; Berman, Katherine; Richardson, Charles; Lien, Hans; Kleanthous, Harry; Mantis, Nicholas J; Joshi, Sangeeta B; Volkin, David B

Informa UK Limited

Medicine; Immunology and Microbiology; Pharmacology, Toxicology and Pharmaceutics

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