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Antigen-adjuvant interactions, stability, and immunogenicity profiles of a SARS-CoV-2 receptor-binding domain (RBD) antigen formulated with aluminum salt and CpG adjuvants.
Bajoria, Sakshi; Kaur, Kawaljit; Kumru, Ozan S; Van Slyke, Greta; Doering, Jennifer; Novak, Hayley; Rodriguez Aponte, Sergio A; Dalvie, Neil C; Naranjo, Christopher A; Johnston, Ryan S; Silverman, Judith Maxwell; Kleanthous, Harry; Love, J Christopher; Mantis, Nicholas J; Joshi, Sangeeta B; Volkin, David B.
Afiliación
  • Bajoria S; Department of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, Lawrence, KS, USA.
  • Kaur K; Department of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, Lawrence, KS, USA.
  • Kumru OS; Department of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, Lawrence, KS, USA.
  • Van Slyke G; Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, NY, USA.
  • Doering J; Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, NY, USA.
  • Novak H; Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, NY, USA.
  • Rodriguez Aponte SA; Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
  • Dalvie NC; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Naranjo CA; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Johnston RS; Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
  • Silverman JM; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Kleanthous H; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Love JC; Bill & Melinda Gates Foundation, Seattle, WA, USA.
  • Mantis NJ; Bill & Melinda Gates Foundation, Seattle, WA, USA.
  • Joshi SB; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Volkin DB; Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
Hum Vaccin Immunother ; 18(5): 2079346, 2022 11 30.
Article en En | MEDLINE | ID: mdl-35666264
Low-cost, refrigerator-stable COVID-19 vaccines will facilitate global access and improve vaccine coverage in low- and middle-income countries. To this end, subunit-based approaches targeting the receptor-binding domain (RBD) of SARS-CoV-2 Spike protein remain attractive. Antibodies against RBD neutralize SARS-CoV-2 by blocking viral attachment to the host cell receptor, ACE2. Here, a yeast-produced recombinant RBD antigen (RBD-L452K-F490W or RBD-J) was formulated with various combinations of aluminum-salt (Alhydrogel®, AH; AdjuPhos®, AP) and CpG 1018 adjuvants. We assessed the effect of antigen-adjuvant interactions on the stability and mouse immunogenicity of various RBD-J preparations. While RBD-J was 50% adsorbed to AH and <15% to AP, addition of CpG resulted in complete AH binding, yet no improvement in AP adsorption. ACE2 competition ELISA analyses of formulated RBD-J stored at varying temperatures (4, 25, 37°C) revealed that RBD-J was destabilized by AH, an effect exacerbated by CpG. DSC studies demonstrated that aluminum-salt and CpG adjuvants decrease the conformational stability of RBD-J and suggest a direct CpG-RBD-J interaction. Although AH+CpG-adjuvanted RBD-J was the least stable in vitro, the formulation was most potent at eliciting SARS-CoV-2 pseudovirus neutralizing antibodies in mice. In contrast, RBD-J formulated with AP+CpG showed minimal antigen-adjuvant interactions, a better stability profile, but suboptimal immune responses. Interestingly, the loss of in vivo potency associated with heat-stressed RBD-J formulated with AH+CpG after one dose was abrogated by a booster. Our findings highlight the importance of elucidating the key interrelationships between antigen-adjuvant interactions, storage stability, and in vivo performance to enable successful formulation development of stable and efficacious subunit vaccines.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: SARS-CoV-2 / COVID-19 Límite: Animals / Humans Idioma: En Revista: Hum Vaccin Immunother Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: SARS-CoV-2 / COVID-19 Límite: Animals / Humans Idioma: En Revista: Hum Vaccin Immunother Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos