Ivelin Georgiev
Last active: 3/14/2018

Two-Component Ferritin Nanoparticles for Multimerization of Diverse Trimeric Antigens.

Georgiev IS, Joyce MG, Chen RE, Leung K, McKee K, Druz A, Van Galen JG, Kanekiyo M, Tsybovsky Y, Yang ES, Yang Y, Acharya P, Pancera M, Thomas PV, Wanninger T, Yassine HM, Baxa U, Doria-Rose NA, Cheng C, Graham BS, Mascola JR, Kwong PD
ACS Infect Dis. 2018 4 (5): 788-796

PMID: 29451984 · DOI:10.1021/acsinfecdis.7b00192

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.

MeSH Terms (12)

Antigens Epitopes Ferritins Gene Products, env HIV-1 HIV Antibodies Humans Models, Molecular Nanoparticles Protein Conformation Protein Multimerization Recombinant Proteins

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