Publications by authors named "B A Fiala"

Article Synopsis
  • Researchers developed a two-component protein nanoparticle vaccine (RBD-NP) displaying the SARS-CoV-2 spike protein, which successfully triggered strong immune responses in clinical trials and has been licensed as SKYCovione.
  • The study examined how mutations from various SARS-CoV-2 variants (B.1.351 and P.1) affect the vaccine's properties, immunogenicity, and potential for variant adaptation, showing substantial differences among variants.
  • By stabilizing the RBD-NPs through specific mutations, the team enhanced vaccine stability without compromising its ability to generate neutralizing antibodies, highlighting RBD-NP’s promise in creating versatile and effective vaccines against emerging coronavirus variants.
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Nanoparticles for multivalent display and delivery of vaccine antigens have emerged as a promising avenue for enhancing B cell responses to protein subunit vaccines. Here, we evaluated B cell responses in rhesus macaques immunized with prefusion-stabilized respiratory syncytial virus (RSV) F glycoprotein trimer compared with nanoparticles displaying 10 or 20 copies of the same antigen. We show that multivalent display skews antibody specificities and drives epitope-focusing of responding B cells.

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Article Synopsis
  • Computationally designed protein nanoparticles are gaining attention as a new platform for creating vaccines and biologics, but they often have trouble being secreted from eukaryotic cells.
  • The research reveals that the design of these nanoparticles can unintentionally create hidden sections that mimic transmembrane domains, hindering their secretion.
  • A new computational tool, called the Degreaser, helps redesign these nanoparticles to eliminate the problematic regions, significantly improving their secretion efficiency while maintaining stability, making them more applicable in biotechnology.
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Nanoparticle vaccines usually prime stronger immune responses than soluble antigens. Within this class of subunit vaccines, the recent development of computationally designed self-assembling two-component protein nanoparticle scaffolds provides a powerful and versatile platform for displaying multiple copies of one or more antigens. Here we report the generation of three different nanoparticle immunogens displaying 60 copies of p67C, an 80 amino acid polypeptide from a candidate vaccine antigen of , and their immunogenicity in cattle.

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Protein nanoparticle scaffolds are increasingly used in next-generation vaccine designs, and several have established records of clinical safety and efficacy. Yet the rules for how immune responses specific to nanoparticle scaffolds affect the immunogenicity of displayed antigens have not been established. Here we define relationships between anti-scaffold and antigen-specific antibody responses elicited by protein nanoparticle immunogens.

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