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AssigneesUniversity of Florida Research Foundation, Inc., Emmune, Inc.
InventorsMichael Farzan, Brian Quinlan, Yan Guo, Huihui Mu, Wenhui He, Hyeryun Choe, Lizhou Zhang, Charles Bailey, Michael Alpert
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The present invention provides scaffolded antigens that have demonstrated improved biochemical and immunogenic properties. The invention also provides engineered SARS-CoV-2 immunogens that contain a modified receptor-binding domain (RBD) sequence. Also provided in the invention are vaccine compositions that contain the scaffolded antigens, including the engineered RBD polypeptides that are fused to the scaffold proteins described herein. The invention also provides methods of using such vaccine compositions in various therapeutic applications, e.g., for preventing or treating SARS-CoV-2 infections.
An engineered antigen or multimer thereof, comprising an altered receptor-binding domain (RBD) sequence of SARS-CoV-2 spike (S) protein that has modifications relative to the wildtype RBD sequence, wherein the modifications comprise mutations at the inter-subunit interfaces of the RBD that result in (a) formation of at least two engineered N-linked glycosylation sites, (b) formation of at least one engineered N-linked glycosylation site and substitution of at least one additional hydrophobic residue at the inter-subunit interface, or (c) formation of at least one engineered N-linked glycosylation site that is formed from two substitutions.
A fusion protein comprising an antigen and a scaffold protein, wherein the scaffold protein is at least 50% (e.g., at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, or at least 98%) identical to amino acids 2-96 of Acidiferrobacteraceae bacterium (Ap) half-ferritin (SEQ ID NO:
A fusion protein comprising an antigen and a scaffold protein, wherein the scaffold protein is at least 50% (e.g., at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, or at least 98%) identical to the F10 protein sequence shown in any one of SEQ ID NOs:169-240.
A fusion protein comprising an antigen and a scaffold protein, wherein (a) the scaffold protein is a self-assembling homo-multimer comprising 10-59 subunits;
A fusion protein comprising an antigen and a scaffold protein, wherein (a) the scaffold protein is a self-assembling homo-multimer comprising 13-59 subunits;
Dependencies are inferred from the claim text.