**1. Introduction**

Hepatitis B is globally one of the most common infectious diseases in humans, which is associated with significant morbidity and mortality. Approximately 2 billion people worldwide have been infected with hepatitis B virus (HBV) and approximately 257 million people live with chronic HBV infections. An estimated 887,000 persons died in 2015 from acute or chronic consequences of hepatitis B [1–4]. The ability of the HBV structural proteins, including the hepatitis B surface (envelope) proteins (HBsAg) to assemble into non-infectious sub-viral particles (SVPs), allows the generation of highly organized particles displaying neutralizing epitopes that promote protective immune responses against the parent virus. The approval of the recombinant hepatitis B vaccine Recombivax HB (Merck Sharp and Dohme) in 1986, based on HBsAg SVPs and produced in the yeast *Saccharomyces cerevisiae*, was the first developed vaccine using recombinant DNA technology. The recombinant vaccine, together with the recombinant products, human insulin (licensed 1982), human growth hormone (licensed 1985), and alpha interferon (licensed 1986), demonstrated the capability of biotechnological approaches to generate innovative medicines [1]. The ability to accept foreign antigenic sequences into the SVP structure can provide the basis for the development of delivery platforms for targeted medically relevant sequences, as in the case of the RTS,S/AS01 (Mosquirix™) vaccine against malaria. The antigenic components of Mosquirix™ are chimeric SVPs containing HBsAg proteins fused to a *Plasmodium*

*falciparum*-specific circumsporozoite (CS) polypeptide [5–7]. The design and generation of chimeric SVPs holds enormous potential in the treatment of infectious diseases, for which there are no effective vaccines [8–10].
