The present disclosure provides compositions and methods for the generation of an antibody or immunogenic composition, such as a vaccine, through epitope focusing by variable effective antigen surface concentration. Generally, the composition and methods of the disclosure comprise three steps: a “design process” comprising one or more in silico bioinformatics steps to select and generate a library of potential antigens for use in the immunogenic composition; a “formulation process”, comprising in vitro testing of potential antigens, using various biochemical assays, and further combining two or more antigens to generate one or more immunogenic compositions; and an “administering” step, whereby the immunogenic composition is administered to a host animal, immune cell, subject or patient. Further steps may also be included, such as the isolation and production of antibodies raised by host immune response to the immunogenic composition.

The present disclosure provides compositions and methods for the generation of an antibody or immunogenic composition, such as a vaccine, through epitope focusing by variable effective antigen surface concentration. Generally, the composition and methods of the disclosure comprise three steps: a “design process” comprising one or more in silico bioinformatics steps to select and generate a library of potential antigens for use in the immunogenic composition; a “formulation process”, comprising in vitro testing of potential antigens, using various biochemical assays, and further combining two or more antigens to generate one or more immunogenic compositions; and an “administering” step, whereby the immunogenic composition is administered to a host animal, immune cell, subject or patient. Further steps may also be included, such as the isolation and production of antibodies raised by host immune response to the immunogenic composition.

Disclosed are methods of a method of making a nanostructure, comprising adding a component A (compA) protein to a solution comprising a component B (compB) protein under conditions that minimize shear stress, thereby forming a compA:compB complex. Further disclosed are methods of making a nanostructure, comprising (i) providing a first inlet fluid stream comprising a first protein and a second inlet fluid stream comprising a second protein, and (ii) contacting the first inlet fluid stream and the second inlet fluid stream to form an outlet stream, wherein mixing of the first protein and the second protein occurs in the outlet stream, thereby forming a protein complex comprises the first protein and the second protein. A microfluidic mixer may be used. The methods may further comprise purifying the compA:compB complex from excess compA, excess compB, and/or other impurities by filtering the solution with a 1,000 kDa membrane or an equivalent thereof.

Disclosed are methods of a method of making a nanostructure, comprising adding a component A (compA) protein to a solution comprising a component B (compB) protein under conditions that minimize shear stress, thereby forming a compA:compB complex. Further disclosed are methods of making a nanostructure, comprising (i) providing a first inlet fluid stream comprising a first protein and a second inlet fluid stream comprising a second protein, and (ii) contacting the first inlet fluid stream and the second inlet fluid stream to form an outlet stream, wherein mixing of the first protein and the second protein occurs in the outlet stream, thereby forming a protein complex comprises the first protein and the second protein. A microfluidic mixer may be used. The methods may further comprise purifying the compA:compB complex from excess compA, excess compB, and/or other impurities by filtering the solution with a 1,000 kDa membrane or an equivalent thereof.

Enhanced virus-like particles (eVLPs), comprising a membrane comprising a phospholipid bilayer with one or more virally-derived glycoproteins on the external side; and a cargo disposed in the core of the eVLP on the inside of the membrane, wherein the eVLP does not comprise an exogenous gag/pol protein, and methods of use thereof for delivery of the cargo to cells.

Enhanced virus-like particles (eVLPs), comprising a membrane comprising a phospholipid bilayer with one or more virally-derived glycoproteins on the external side; and a cargo disposed in the core of the eVLP on the inside of the membrane, wherein the eVLP does not comprise an exogenous gag/pol protein, and methods of use thereof for delivery of the cargo to cells.

The invention is directed to a bispecific chimeric antigen receptor, comprising: (a) at least two antigen-specific targeting regions; (b) an extracellular spacer domain; (c) a transmembrane domain; (d) at least one co-stimulatory domain; and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and wherein the bispecific chimeric antigen receptor is co-expressed with a therapeutic control. The invention also provides methods and uses of the bispecific chimeric antigen receptors.

The invention is directed to a bispecific chimeric antigen receptor, comprising: (a) at least two antigen-specific targeting regions; (b) an extracellular spacer domain; (c) a transmembrane domain; (d) at least one co-stimulatory domain; and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and wherein the bispecific chimeric antigen receptor is co-expressed with a therapeutic control. The invention also provides methods and uses of the bispecific chimeric antigen receptors.

Described herein are Zika virus vaccines and compositions and methods of producing and administering said vaccines to subjects in need thereof.

Described herein are Zika virus vaccines and compositions and methods of producing and administering said vaccines to subjects in need thereof.