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

Volpatti, L. R.; Wallace, R. P.; Cao, S.; Raczy, M.; Wang, R.; Gray, L. T.; Alpar, A. T.; Briquez, P. S.; Mitrousis, N.; Marchell, T. M.; Sasso, M. S.; Nguyen, M.; Mansurov, A.; Budina, E.; Solanki, A.; Watkins, E. A.; Schnorenberg, M. R.; Tremain, A. C.; Reda, J. W.; Nicolaescu, V.; Furlong, K.; Dvorkin, S.; Yu, S. S.; Manicassamy, B.; LaBelle, J. L.; Tirrell, M. V.; Randall, G.; Kwissa, M.; Swartz, M.; Hubbell, J.

doi:10.1101/2021.04.08.438884

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bioRxiv · 10.1101/2021.04.08.438884

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

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Abstract

A diverse portfolio of SARS-CoV-2 vaccine candidates is needed to combat the evolving COVID-19 pandemic. Here, we developed a subunit nanovaccine by conjugating SARS-CoV-2 Spike protein receptor binding domain (RBD) to the surface of oxidation-sensitive polymersomes. We evaluated the humoral and cellular responses of mice immunized with these surface-decorated polymersomes (RBDsurf) 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 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.

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Volpatti, L. R., Wallace, R. P., Cao, S., Raczy, M., Wang, R., Gray, L. T., Alpar, A. T., Briquez, P. S., Mitrousis, N., Marchell, T. M., Sasso, M. S., Nguyen, M., Mansurov, A., Budina, E., Solanki, A., Watkins, E. A., Schnorenberg, M. R., Tremain, A. C., Reda, J. W., Nicolaescu, V., Furlong, K., Dvorkin, S., Yu, S. S., Manicassamy, B., LaBelle, J. L., Tirrell, M. V., Randall, G., Kwissa, M., Swartz, M., Hubbell, J.. 2021-04-08. Polymersomes decorated with SARS-CoV-2 spike protein receptor binding domain elicit robust humoral and cellular immunity. https://doi.org/10.1101/2021.04.08.438884

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