Two-Component Ferritin Nanoparticles for Multimerization of Diverse Trimeric Antigens.
Antigen multimerization on a nanoparticle can result in improved neutralizing antibody responses. A platform that has been successfully used for displaying antigens from a number of different viruses is ferritin, a self-assembling protein nanoparticle that allows the attachment of multiple copies (24 monomers or 8 trimers) of a single antigen. Here, we design two-component ferritin variants that allow the attachment of two different antigens on a single particle in a defined ratio and geometric pattern. The two-component ferritin was specifically designed for trimeric antigens, accepting four trimers per particle for each antigen, and was tested with antigens derived from HIV-1 envelope (Env) and influenza hemagglutinin (HA). Particle formation and the presence of native-like antigen conformation were confirmed through negative-stain electron microscopy and antibody-antigen binding analysis. Immunizations in guinea pigs with two-component ferritin particles, displaying diverse Env, HA, or both antigens, elicited neutralizing antibody responses against the respective viruses. The results provide proof-of-principle for the self-assembly of a two-component nanoparticle as a general technology for multimeric presentation of trimeric antigens.
Duke Scholars
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Related Subject Headings
- Recombinant Proteins
- Protein Multimerization
- Protein Conformation
- Nanoparticles
- Models, Molecular
- Humans
- HIV-1
- HIV Antibodies
- Gene Products, env
- Ferritins
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Recombinant Proteins
- Protein Multimerization
- Protein Conformation
- Nanoparticles
- Models, Molecular
- Humans
- HIV-1
- HIV Antibodies
- Gene Products, env
- Ferritins