Broadly neutralizing antibody-templated divalent immunogen vaccines
AssigneeUniversity of Hawaii
InventorsIain MACPHERSON, Ryan BAILEY, Axel LEHRER
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Abstract
The present disclosure relates generally to divalent immunogens comprising a scaffold and two antigens or epitopes thereof, multimers, compositions, and methods of using the same. Such divalent immunogens are useful, for example, for stimulating an immune response.
Claims75
A divalent immunogen comprising:
- (a) a scaffold, and
- (b) two antigens or epitopes thereof;
- wherein each antigen or epitope thereof is covalently linked to the scaffold.
A polynucleotide encoding a scaffold or portion thereof, wherein the encoded scaffold provides precise positioning of two antigens or epitopes thereof such that only certain B-cell receptors are preferably bound to both antigens simultaneously.
A method of identifying antibodies with preferred characteristics for divalent immunogens, comprising:
- (a) providing a divalent immunogen comprising a known broadly neutralizing antibody and an antigen or epitope thereof;
- (b) administering the divalent immunogen to a subject, optionally a mouse;
- (c) Isolating B cells from the subject;
- (d) screening the isolated B cells for ability to bind to the divalent immunogen in high avidity, bidentate fashion;
- and
- (e) sequencing the complementarity determining regions of B cells that bind as in (d).
A method of forming a ring structure comprising the divalent immunogen of any one of class 1-54 and a B-cell receptor and/or antibody;
- wherein the divalent immunogen comprises a specific antigenic spacing that allows the B-cell receptor and/or antibody to bind with a Fab-Fab angle of about 20 degrees to about 150 degrees.
Dependencies are inferred from the claim text.