Red Alga Porphyridium Supports High‐Yield Production of a Functional Chimeric Hepatitis B Surface Antigen With Strong Cellular and Humoral Immunogenicity

Microalgae represent promising production factories for the light-driven, cost-effective production of recombinant proteins. The red microalga Porphyridium purpureum displays particularly favourable transgene expression properties due to the episomal maintenance of transformation vectors at high copy numbers in the nucleus. In this work, we explored the potential of Porphyridium purpureum to synthesise a candidate vaccine against Hepatitis B virus (HBV). We show high-yield expression of an HBV chimeric surface antigen and efficient assembly of virus-like particles (VLPs) in algal cells. We established a purification protocol for the VLPs and conducted vaccination studies in experimental animals. The results demonstrate that the alga-produced HBV antigen elicits superior humoral and cellular immune responses compared to a commercial HBV vaccine produced in yeast. The antigen triggers virus-neutralising antibodies against different HBV variants, including vaccine-escape mutations that evade the immune response to current vaccines in humans. Our work establishes Porphyridium as a highly promising production platform for vaccines and other proteinaceous biopharmaceuticals.