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.
Highlights
Hepatitis B is globally one of the most common infectious diseases in humans, which is associated with significant morbidity and mortality
The development of preventative vaccines against hepatitis B resulted in remarkable advances in reducing hepatitis B virus (HBV) associated liver diseases
Chronic hepatitis B is still difficult to control due to continuous viral replication driven by the episomal closed circular DNA (cccDNA) present in the nuclei of infected hepatocytes
Summary
Hepatitis B is globally one of the most common infectious diseases in humans, which is associated with significant morbidity and mortality. SVPs represent effective immunogens for the induction virion formation depends on the presence of the viral capsid containing rcDNA and the the of a protective immune response [26,27,28]. HBV virion formation depends on the presence of the viral capsid containing rcDNA and the HBsAg proteins for envelopment. The preS1 region of HBsAgL is essential for the assembly of infectious HBV particles by interacting with the capsid [17,33], possibly contributes to the binding to a proteoglycan attachment site [34,35], and is required for binding to the hepatocyte entry receptor, sodium taurochlorate cotransporting polypeptide (NTCP) [36,37]. SVPs and virions, but they have identical antigenic structures due to the S-domain, which is encoded by all HBV envelope proteins (Figure 1A,B)
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