Polymersomes as Stable Nanocarriers for a Highly Immunogenic and Durable SARS-CoV-2 Spike Protein Subunit Vaccine

Posted: 2021 Oct 26;15(10)
doi: 10.1021/acsnano.1c01243 · PMID: 34618423 · PMCIDPMC8525042

Authors: Jian Hang Lam 1, Amit K Khan 1, Thomas A Cornell 1, Teck Wan Chia 1, Regine J Dress 2, Wen Wang William Yeow 1, Nur Khairiah Mohd-Ismail 3, Shrinivas Venkataraman 1, Kim Tien Ng 3, Yee-Joo Tan 3 4, Danielle E Anderson 5, Florent Ginhoux 2 6, Madhavan Nallani 1


Multiple successful vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed to address the ongoing coronavirus disease 2019 (Covid-19) pandemic. In the present work, we describe a subunit vaccine based on the SARS-CoV-2 spike protein coadministered 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 poly(butadiene)-b-poly(ethylene 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 (DC1 and DC2), which are key initiators of the adaptive immune response. Two doses of our formulation elicit robust neutralizing antibody titers in C57BL/6 mice that persist at least 40 days. Furthermore, we confirm the presence of functional memory CD4+ and CD8+ T cells that produce T helper type 1 cytokines. This study is an important step toward the development of an efficacious vaccine in humans.

Keywords: ACM; Covid-19; neutralizing antibody; polymersome; spike; vaccine.

Conflict of interest statement

The authors declare the following competing financial interest(s): D.E.A. developed the cPass kit; J.H.L, A.K.K., T.A.C., T.W.C., W.W.W.Y., S.V., and M.N. are employees of ACM Biolabs Pte Ltd; F.G. is part of the ACM SAB.