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

Lisa R Volpatti, Rachel P Wallace, Shijie Cao, Michal M Raczy, Ruyi Wang, Laura T Gray, Aaron T Alpar, Priscilla S Briquez, Nikolaos Mitrousis, Tiffany M Marchell, …
bioRxiv : the preprint server for biology
04/08/2021
DOI: 10.1101/2021.04.08.438884
PMCID: PMC8043456
PMID: 33851166
url
https://doi.org/10.1101/2021.04.08.438884View
Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

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 (RBD ) compared to RBD-encapsulated polymersomes (RBD ) and unformulated RBD (RBD ), using monophosphoryl lipid A-encapsulated polymersomes (MPLA PS) as an adjuvant. While all three groups produced high titers of RBD-specific IgG, only RBD elicited a neutralizing antibody response to SARS-CoV-2 comparable to that of human convalescent plasma. Moreover, RBD was the only group to significantly increase the proportion of RBD-specific germinal center B cells in the vaccination-site draining lymph nodes. Both RBD and RBD 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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