A shared N-terminal hydrophobic tail for the formation of nanoparticulates.

Abstract

Nanoparticulate design is important for the production of nanotechnological materials and passive immunogens. Using lessons from our hepatitis E vaccine, we herein design protein-based nanoparticles through incorporation of an N-terminal hydrophobic tail (NHT, located on HEV ORF2 aa368-460). Flu HA1, HIV gp41/gp120/p24, HBsAg and HPV16 L2 were fused with NHT, expressed in Escherichia coli and subjected to self-assembly in vitro. Nanosized particles were characterized by size-exclusion chromatography and negative electron microscopy. Immunogenicity was assessed in mice. All the NHT-fused proteins spontaneously formed nanoparticulates and presented with immunogenicity approximately 2-log over their nonassembling forms. Protein self-assembly provides an attractive means to create nanosized particles that bear specific antigens. Our strategy outlines a novel and shared method for the design of immunogenic nanoparticles.