Two-component vaccine consisting of virus-like particles displaying hepatitis C virus envelope protein 2 oligomers

Abstract

Development of B-cell-based hepatitis C virus (HCV) vaccines that induce broadly neutralizing antibodies (bNAbs) is hindered by extensive sequence diversity and low immunogenicity of envelope glycoprotein vaccine candidates, most notably soluble E2 (sE2). To overcome this, we employed two-component approaches using self-assembling virus-like particles (cVLPs; component 1), displaying monomeric or oligomeric forms of HCV sE2 (sE2mono or sE2oligo; component 2). Immunization studies were performed in BALB/c mice and the neutralizing capacity of vaccine-induced antibodies was tested in cultured-virus-neutralizations, using HCV of genotypes 1–6. sE2-cVLP vaccines induced significantly higher levels of NAbs (p = 0.0065) compared to corresponding sE2 vaccines. Additionally, sE2oligo-cVLP was superior to sE2mono-cVLP in inducing bNAbs. Interestingly, human monoclonal antibody AR2A had reduced binding in ELISA to sE2oligo-cVLP compared with sE2mono-cVLP and competition ELISA using mouse sera from vaccinated animals indicated that sE2oligo-cVLP induced significantly less non-bNAbs AR2A (p = 0.0043) and AR1B (p = 0.017). Thus, cVLP-displayed oligomeric sE2 shows promise as an HCV vaccine candidate.

Potential Applications of Thermophilic Bacteriophages in One Health

“…In addition to this, they have also been used as platforms to display and enhance the immunogenicity of lessimmunogenic peptide antigens from other infectious agents. The display of foreign peptides on the surface of VLPs enhances the immunogenicity of the peptides and offers protection against infection by the infectious agents from which the peptides were derived [32,[50][51][52]. However, VLPs derived from mesophilic viruses have some limitations.…”

Capsid virus-like particle display improves recombinant influenza neuraminidase antigen stability and immunogenicity in mice

“…Bioconjugation approaches like the Tag/Catcher AP205 cVLP system can covalently couple large structurally complex antigens onto cVLPs in a controlled and directional manner. 31 , 35 , 41 , 42 Similar to SpyCatcher-SpyTag, 43 this system relies on a split-protein conjugation where the antigen is expressed with a short peptide Tag that rapidly forms an irreversible isopeptide bond upon association with a Catcher binding partner. On AP205, Catchers are evenly distributed on the surface to present conjugated antigens in a uniform orientation that mimics the multivalent display on a virus.…”