Next generation vaccine platform: polymersomes as stable nanocarriers for a highly immunogenic and durable SARS-CoV-2 spike protein subunit vaccine

Lam, Jian Hang; Khan, Amit Kumar; Cornell, Thomas Andrew; Dress, Regine Josefine; Chia, Teck Wan; William Yeow, Wen Wang; Mohd-Ismail, Nur Khairiah; Venkatraman, Shrinivas; Ng, Kim Tien; Tan, Yee-Joo; Anderson, Danielle E.; Ginhoux, Florent; Nallani, Madhavan

Multiple successful vaccines against SARS-CoV-2 are urgently needed to address the ongoing Covid-19 pandemic. In the present work, we describe a subunit vaccine based on the SARS-CoV-2 spike protein co-administered with CpG adjuvant. To enhance the immunogenicity of our formulation, both antigen and adjuvant were encapsulated with our proprietary artificial cell membrane (ACM) polymersome technology. Structurally, ACM polymersomes are self-assembling nanoscale vesicles made up of an amphiphilic block copolymer comprising of polybutadiene-b-polyethylene glycol and a cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane. Functionally, ACM polymersomes serve as delivery vehicles that are efficiently taken up by dendritic cells, which are key initiators of the adaptive immune response. Two doses of our formulation elicit robust neutralizing titers in C57BL/6 mice that persist at least 40 days. Furthermore, we confirm the presence of memory CD4+ and CD8+ T cells that produce Th1 cytokines. This study is an important step towards the development of an efficacious vaccine in humans.