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Production of E. coli-expressed Self-Assembling Protein Nanoparticles for Vaccines Requiring Trimeric Epitope Presentation
Published on: August 21, 2019
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Epitope targeting with self-assembled peptide vaccines.
David F Zeigler1, Emily Gage1, Richard Roque1,2
11TRIA Bioscience Corp, Suite 260, 1616 Eastlake Avenue East, Seattle, WA 98102 USA.
NPJ Vaccines
|July 26, 2019
Summary
A novel nanoparticle vaccine platform simplifies development by directly incorporating B cell epitopes. This new platform successfully generated antibodies against targets for fertility, allergy, and influenza in mice.
Area of Science:
- Vaccinology
- Nanotechnology
- Immunology
Background:
- Nanoparticle delivery systems accelerate vaccine development.
- A previously described 61-amino acid carrier forms coiled-coil nanoparticles.
- This carrier can be functionalized with T cell epitopes.
Purpose of the Study:
- To expand the utility of the nanoparticle carrier by appending B cell epitopes.
- To create a simplified vaccine platform eliminating traditional conjugation.
- To test the efficacy of this new platform in preclinical models.
Main Methods:
- Appending B cell epitopes (Tau, amyloid-β, GnRH, IgE, influenza HA stem) to the nanoparticle carrier.
- Characterizing particle assembly using biophysical techniques (CD, AUC, DLS).
- Evaluating vaccine efficacy in outbred mice against multiple targets.
Main Results:
- Peptides assembled into ~20 nm particles and induced antibody responses.
- Vaccines targeting gonadotropin-releasing hormone reduced fertility in male mice.
- Anti-IgE antibodies reduced free IgE and prevented anaphylaxis.
- Influenza HA stem epitope antibodies protected against lethal H1N1 challenge.
Conclusions:
- The nanoparticle platform efficiently elicits antibodies against various B cell epitopes.
- This approach simplifies vaccine development and conjugation.
- The platform shows promise for prophylactic and therapeutic applications.
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