Polymersomes Decorated with the SARS-CoV‑2 Spike Protein Receptor-Binding Domain Elicit Robust Humoral and Cellular Immunity

• Published in: ACS central science 2021-08, Vol.7 (8), p.1368-1380
• Main Authors: Volpatti, Lisa R, Wallace, Rachel P, Cao, Shijie, Raczy, Michal M, Wang, Ruyi, Gray, Laura T, Alpar, Aaron T, Briquez, Priscilla S, Mitrousis, Nikolaos, Marchell, Tiffany M, Sasso, Maria Stella, Nguyen, Mindy, Mansurov, Aslan, Budina, Erica, Solanki, Ani, Watkins, Elyse A, Schnorenberg, Mathew R, Tremain, Andrew C, Reda, Joseph W, Nicolaescu, Vlad, Furlong, Kevin, Dvorkin, Steve, Yu, Shann S, Manicassamy, Balaji, LaBelle, James L, Tirrell, Matthew V, Randall, Glenn, Kwissa, Marcin, Swartz, Melody A, Hubbell, Jeffrey A
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Chemistry; INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
• ISSN: 2374-7943; 2374-7951
• DOI: 10.1021/acscentsci.1c00596

The COVID-19 pandemic underscores the need for rapid, safe, and effective vaccines. In contrast to some traditional vaccines, nanoparticle-based subunit vaccines are particularly efficient in trafficking antigens to lymph nodes, where they induce potent immune cell activation. Here, we developed a strategy to decorate the surface of oxidation-sensitive polymersomes with multiple copies of the SARS-CoV-2 spike protein receptor-binding domain (RBD) to mimic the physical form of a virus particle. We evaluated the vaccination efficacy of these surface-decorated polymersomes (RBDsurf) in mice compared to RBD-encapsulated polymersomes (RBDencap) and unformulated RBD (RBDfree), using monophosphoryl-lipid-A-encapsulated polymersomes (MPLA PS) as an adjuvant. While all three groups produced high titers of RBD-specific IgG, only RBDsurf elicited a neutralizing antibody response to SARS-CoV-2 comparable to that of human convalescent plasma. Moreover, RBDsurf was the only group to significantly increase the proportion of RBD-specific germinal center B cells in the vaccination-site draining lymph nodes. Both RBDsurf and RBDencap drove similarly robust CD4+ and CD8+ T cell responses that produced multiple Th1-type cytokines. We conclude that a multivalent surface display of spike RBD on polymersomes promotes a potent neutralizing antibody response to SARS-CoV-2, while both antigen formulations promote robust T cell immunity.