Chimeric hepatitis E virus-like particle as a carrier for oral-delivery

Abstract

Oral delivery with virus-like particles (VLPs) is advantageous because of the inherited entry pathway from their parental viral capsids, which enables VLP to withstand the harsh and enzymatic environment associated with human digestive tract. However, the repeat use of this system is challenged by the self-immunity. In order to overcome this problem, we engineered the recombinant capsid protein of hepatitis E virus by inserting p18 peptide, derived from the V3 loop of HIV-1 gp120, into the antibody-binding site. The chimeric VLP resembled the tertiary and quaternary structures of the wild type VLP and specifically reacted with an HIV-1 antibody against V3 loop. Different from the wild type VLP, the chimeric VLP was vulnerable to trypsin cleavage although it appeared as intact particle, suggesting that the intermolecular forces of attraction between the recombinant capsid proteins are strong enough to maintain the VLP icosahedral arrangement. Importantly, this VLP containing the V3 loop did not react with anti-HEV antibodies, in correspondence to the mutation at its antibody-binding site. Therefore, the insertion of peptides at the surface antigenic site could allow VLPs to escape pre-existing anti-HEV humoral immunity.

A Study on the Virus-Like Particle Formation of Hepatitis E Virus ORF2 and Rotavirus NSP4 Protein in the Eukaryotic and Prokaryotic Expression Systems

“…Previous studies have shown that the insertion of a peptide at C-terminal of HEV not only affects self-assembling of VLP formation, but also helps the produced VLP be used as carrier for other antigens (21,22). Our results in agreement with previous reports showed that the OSU-a strain of Rotavirus NSP4 was successfully linked to C-terminal of the truncated ORF2 to assemble to VLP.…”

Nodavirus-based biological container for targeted delivery system

“…Induction of mucosal immunity through oral vaccine administration is benefi cial due to its convenience; however, there are several diffi culties in oral immunization with non-replicating molecules such as proteolytic enzymes in the gastrointestinal tract and an acidic environment. VLPs derived from harmful human viruses such as the hepatitis-E virus-like particle (HEV-VLP) have previously been found to be tolerant and still intact after exposure to digestive juices (Jariyapong et al 2013). Th is is because the quaternary arrangement of VLP protein protects it from the cleavage of protease enzymes.…”

Chemically Activatable Viral Capsid Functionalized for Cancer Targeting

“…Particles were then manually selected and initially center and orientation was determined by reference-dependent cross-correlation by using a density of the wild-type HEV-VLP [19] as our initial model. Polar Fourier transformation algorithm [20] was used to iteratively carry out origin and orientation refinement.…”

“…Moreover, it can accommodate sequence modification at P-domain without interference with HEV-VLP assembly. Genetically engineered chimeric VLPs having modifications in the somewhat isolated protrusion domain, are as stable as wild-type VLPs [9], and like the HEV virion, can tolerate extreme pH values and intestinal proteases [10]. This has exciting implications for an orally deliverable chemotherapeutic agent.…”