The emergence of the SARS-CoV-2 virus and its immune-escaping variants have led to global COVID-19 pandemic/endemic, underscoring the urgent need for effective vaccines with strong and durable immune responses.

Researchers at the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID) used a novel approach to SARS-CoV-2 vaccine development by leveraging hepatitis B surface antigen (HBsAg), which has a proven track record of safety and efficacy in hepatitis B vaccines. They designed fusion protein constructs comprised of HBsAg linked by a series of glycine-serine residues to the prefusion stabilized spike protein of SARS-CoV-2. These constructs can self-assemble into nanoparticles in mammalian cells and bind monoclonal antibodies (mAbs) that are specific to different domains of the SARS-CoV-2 spike. The nanoparticles elicit potent and durable immune responses including neutralizing antibody response. In vitro and in vivo experiments demonstrate that this nanoparticle platform has the potential for use as a robust SARS-CoV-2 vaccine.