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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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Two-Component Ferritin Nanoparticles for Multimerization of Diverse Trimeric Antigens
Ivelin S Georgiev1, Michael Gordon Joyce1, Rita E Chen1
1Vaccine Research Center, National Institute of Allergy and Infectious Diseases , National Institutes of Health , 40 Convent Drive , Bethesda , Maryland 20892 , United States.
ACS Infectious Diseases
|February 17, 2018
Summary
Researchers developed a novel two-component ferritin nanoparticle capable of displaying multiple distinct viral antigens. This platform enhances neutralizing antibody responses against viruses like HIV-1 and influenza.
Area of Science:
- Biotechnology
- Immunology
- Structural Biology
Background:
- Multimerizing viral antigens on nanoparticles can enhance neutralizing antibody responses.
- Ferritin, a self-assembling protein nanoparticle, has been utilized to display multiple copies of a single antigen.
- Existing ferritin platforms are limited to displaying a single type of antigen per particle.
Purpose of the Study:
- To design and characterize two-component ferritin nanoparticles capable of displaying two different antigens simultaneously in a defined ratio and pattern.
- To evaluate the immunogenicity and efficacy of these novel nanoparticles in eliciting neutralizing antibody responses.
- To establish a generalizable platform for multimeric presentation of trimeric antigens.
Main Methods:
- Design of two-component ferritin variants engineered for specific attachment of trimeric antigens (HIV-1 Env and influenza HA).
- Confirmation of particle formation and native-like antigen conformation using negative-stain electron microscopy and antibody-antigen binding assays.
- Immunization of guinea pigs with single-antigen and dual-antigen two-component ferritin particles, followed by assessment of neutralizing antibody titers.
Main Results:
- Successful self-assembly of two-component ferritin nanoparticles displaying specific geometric arrangements of trimeric antigens.
- Demonstration of native-like antigen conformation and effective antibody binding to displayed antigens.
- Elicitation of significant neutralizing antibody responses against HIV-1 and influenza viruses in immunized animals, including responses to dual-antigen particles.
Conclusions:
- Proof-of-principle for a two-component ferritin nanoparticle platform enabling controlled display of multiple trimeric antigens.
- The developed platform shows potential for generating enhanced multivalent vaccines against various viral pathogens.
- This technology offers a versatile approach for advancing nanoparticle-based vaccine design and antigen presentation strategies.
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