Volpatti, LR; Wallace, RP; Cao, S; Raczy, MM; Wang, R; Gray, LT; Alpar, AT; Briquez, PS; Mitrousis, N; Marchell, TM; Sasso, MS; Nguyen, M; Mansurov, A; Budina, E; Solanki, A; Watkins, EA; Schnorenberg, MR; Tremain, AC; Reda, JW; Nicolaescu, V; Furlong, K; Dvorkin, S; Yu, SS; Manicassamy, B; Labelle, JL; Tirrell, MV; Randall, G; Kwissa, M; Swartz, MA; Hubbell, JA
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.
