Polymersomes decorated with the SARS-CoV-2 spike protein receptor-binding domain elicit robust humoral and cellular immunity

LR Volpatti, RP Wallace, S Cao, MM Raczy… - ACS central …, 2021 - ACS Publications
ACS central science, 2021ACS Publications
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 …
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.
ACS Publications
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