@article {Volpatti2021.04.08.438884, author = {Lisa R. Volpatti and Rachel P. Wallace and Shijie Cao and Michal M. Raczy and Ruyi Wang and Laura T. Gray and Aaron T. Alpar and Priscilla S. Briquez and Nikolaos Mitrousis and Tiffany M. Marchell and Maria Stella Sasso and Mindy Nguyen and Aslan Mansurov and Erica Budina and Ani Solanki and Elyse A. Watkins and Mathew R. Schnorenberg and Andrew C. Tremain and Joseph W. Reda and Vlad Nicolaescu and Kevin Furlong and Steve Dvorkin and Shann S. Yu and Balaji Manicassamy and James L. LaBelle and Matthew V. Tirrell and Glenn Randall and Marcin Kwissa and Melody A. Swartz and Jeffrey A. Hubbell}, title = {Polymersomes decorated with SARS-CoV-2 spike protein receptor binding domain elicit robust humoral and cellular immunity}, elocation-id = {2021.04.08.438884}, year = {2021}, doi = {10.1101/2021.04.08.438884}, publisher = {Cold Spring Harbor Laboratory}, 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.Competing Interest StatementM.A.S. and J.A.H. have patents related to the polymersome technology and interests in LantaBio, which has licensed those patents.}, URL = {https://www.biorxiv.org/content/early/2021/04/08/2021.04.08.438884}, eprint = {https://www.biorxiv.org/content/early/2021/04/08/2021.04.08.438884.full.pdf}, journal = {bioRxiv} }