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

Autor: Volpatti LR; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, United States., Wallace RP; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, United States., Cao S; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, United States., Raczy MM; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, United States., Wang R; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, United States., Gray LT; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, United States., Alpar AT; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, United States., Briquez PS; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, United States., Mitrousis N; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, United States., Marchell TM; Committee on Immunology, University of Chicago, Chicago, IL 60637, United States., Sasso MS; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, United States., Nguyen M; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, United States., Mansurov A; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, United States., Budina E; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, United States., Solanki A; Animal Resources Center, University of Chicago, Chicago, IL 60637, United States., Watkins EA; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, United States., Schnorenberg MR; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, United States., Tremain AC; Committee on Immunology, University of Chicago, Chicago, IL 60637, United States., Reda JW; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, United States., Nicolaescu V; Department of Microbiology, Howard T. Ricketts Laboratory, University of Chicago, Chicago, IL 60637, United States., Furlong K; Department of Microbiology, Howard T. Ricketts Laboratory, University of Chicago, Chicago, IL 60637, United States., Dvorkin S; Department of Microbiology, Howard T. Ricketts Laboratory, University of Chicago, Chicago, IL 60637, United States., Yu SS; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, United States., Manicassamy B; Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, United States., LaBelle JL; Department of Pediatrics, University of Chicago Comer Children's Hospital, Chicago, IL 60637, United States., Tirrell MV; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, United States.; Materials Science Division, Argonne National Laboratory, Lemont, IL 60439, United States., Randall G; Department of Microbiology, Howard T. Ricketts Laboratory, University of Chicago, Chicago, IL 60637, United States., Kwissa M; Department of Microbiology, Howard T. Ricketts Laboratory, University of Chicago, Chicago, IL 60637, United States.; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, United States., Swartz MA; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, United States.; Committee on Immunology, University of Chicago, Chicago, IL 60637, United States.; Ben May Department of Cancer Research, University of Chicago, Chicago, IL 60637, United States.; Committee on Cancer Biology, University of Chicago, Chicago, IL 60637, United States., Hubbell JA; Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL 60637, United States.; Committee on Immunology, University of Chicago, Chicago, IL 60637, United States.; Committee on Cancer Biology, University of Chicago, Chicago, IL 60637, United States.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2021 Apr 08. Date of Electronic Publication: 2021 Apr 08.
DOI: 10.1101/2021.04.08.438884
Abstrakt: 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 surf ) compared to RBD-encapsulated polymersomes (RBD encap ) and unformulated RBD (RBD free ), using monophosphoryl lipid A-encapsulated polymersomes (MPLA PS) as an adjuvant. While all three groups produced high titers of RBD-specific IgG, only RBD surf elicited a neutralizing antibody response to SARS-CoV-2 comparable to that of human convalescent plasma. Moreover, RBD surf 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 surf and RBD encap 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 Interests: COMPETING INTERESTS M.A.S. and J.A.H. have patents related to the polymersome technology and interests in LantaBio, which has licensed those patents.
Databáze: MEDLINE
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