Hepatitis B Virus (HBV) Subviral Particles as Protective Vaccines and Vaccine Platforms

Abstract

Hepatitis B remains one of the major global health problems more than 40 years after the identification of human hepatitis B virus (HBV) as the causative agent. A critical turning point in combating this virus was the development of a preventative vaccine composed of the HBV surface (envelope) protein (HBsAg) to reduce the risk of new infections. The isolation of HBsAg sub-viral particles (SVPs) from the blood of asymptomatic HBV carriers as antigens for the first-generation vaccines, followed by the development of recombinant HBsAg SVPs produced in yeast as the antigenic components of the second-generation vaccines, represent landmark advancements in biotechnology and medicine. The ability of the HBsAg SVPs to accept and present foreign antigenic sequences provides the basis of a chimeric particulate delivery platform, and resulted in the development of a vaccine against malaria (RTS,S/AS01, MosquirixTM), and various preclinical vaccine candidates to overcome infectious diseases for which there are no effective vaccines. Biomedical modifications of the HBsAg subunits allowed the identification of strategies to enhance the HBsAg SVP immunogenicity to build potent vaccines for preventative and possibly therapeutic applications. The review provides an overview of the formation and assembly of the HBsAg SVPs and highlights the utilization of the particles in key effective vaccines.

Recombinant Baculovirus-Produced Grass Carp Reovirus Virus-Like Particles as Vaccine Candidate That Provides Protective Immunity against GCRV Genotype II Infection in Grass Carp

“…The generation of VLPs was first described with the reconstitution of the tobacco mosaic virus (TMV) in 1955 [ 15 ]. Since then, VLPs have become unique entities in the vaccine development strategies [ 16 ]. The VLPs self-assemble structures by one or several viral structural proteins; therefore the risk of a viral replication can be fully avoided [ 17 ].…”

The Case for Exploiting Cross-Species Epitopes in Malaria Vaccine Design

“…Only one licensed vaccine exists, RTS,S, and this vaccine is currently undergoing pilot roll-out in several African countries. The target of RTS,S is the surface circumsporozoite surface protein (CSP) that is expressed on the surface of P. falciparum sporozoites (3). While this vaccine aims to prevent liver stage infection, the results from earlier vaccine trials suggest good immunity in the first six months but then a significant waning of immunity over time, resulting in poor long-term vaccine efficacy (3).…”

“…The target of RTS,S is the surface circumsporozoite surface protein (CSP) that is expressed on the surface of P. falciparum sporozoites (3). While this vaccine aims to prevent liver stage infection, the results from earlier vaccine trials suggest good immunity in the first six months but then a significant waning of immunity over time, resulting in poor long-term vaccine efficacy (3). This is likely due in part to the low dose of sporozoites inoculated by mosquitoes that fails to reactivate memory B-cells, combined with antigenic polymorphisms in the T-cell epitopes of the CSP (4).…”

The impact of size on particle drainage dynamics and antibody response

“…For example, human papilloma viruses (HPVs) are T=7 of ~60nm in size (10), while hepatitis E virus (HEV) VLPs are T=1 of ~25nm (11). The different generations of hepatitis B virus (HBV) vaccines show highly organized sub-viral particles (SVPs) of ~20-25nm (12). In contrast, the arrangement of CPs of VLPs in helical or rod-shape geometry is also possible; tobacco-mosaic virus (TMV) is a well characterized representative of this category.…”