MULTIVALENT CARRIERS AND RELATED VACCINE COMPOSITIONS
Disclosed herein include multivalent carriers comprising a plurality of heterologous coronavirus proteins antigens derived from different coronaviruses . The multivalent carriers herein described can elicit heterologous binding and neutralization properties against coronaviruses that differ from the coronaviruses from which the coronavirus antigens are derived to produce the multivalent carriers. Also provided herein include vaccine compositions comprising the multivalent carriers and related methods using the vaccine compositions in various therapeutic and prophylactic applications.
1 . A method of obtaining a B cell producing a cross-reactive antibody, comprising:
immunizing a mammal with a vaccine composition comprising a multivalent carrier displaying a first plurality of antigens; and
isolating one or more B-cells from said mammal capable of binding a second plurality of antigens, thereby obtaining a b cell producing a cross-reactive antibody.
2 . The method of claim 1 , wherein at least one antigen of the first plurality of antigens and the second plurality of antigens is shared.
3 . The method of claim 1 , wherein at least one antigen of the first plurality of antigens and the second plurality of antigens is different.
4 . The method of claim 1 , wherein the second plurality of antigens comprises a subset of the first plurality of antigens.
5 . (canceled)
6 . The method of claim 1 , wherein the first plurality of antigens and/or the second plurality of antigens are viral polypeptides.
7 . The method of claim 1 , wherein the first plurality of antigens and/or the second plurality of antigens comprise viral polypeptides of a same protein type.
8 . The method of claim 1 , wherein the first plurality of antigens and/or the second plurality of antigens comprise viral polypeptides of a different protein types.
9 . The method of claim 1 , wherein the first plurality of antigens and/or the second plurality of antigens comprises a first viral polypeptide of a first virus and a second viral polypeptide of a second virus that is different from the first virus.
10 .- 13 . (canceled)
14 . The method of claim 1 , wherein the multivalent carrier comprises a nanoparticle selected from the group consisting of: lipid-based nanoparticles, polymeric nanoparticles, inorganic nanoparticles, surfactant-based emulsions, nanowires, silica nanoparticles, virus-like particles, peptide or protein-based particles, lipid-polymer particles, nanolipoprotein particles, and combinations thereof.
15 .- 26 . (canceled)
27 . The method of claim 1 , wherein the method comprises administering the vaccine composition to the mammal two or more times.
28 . The method of claim 1 , wherein the isolating step is performed about 1 day, 2 days, 4 days, 1 week, 10 days, 2 weeks, 3 weeks, 4weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, or 10 weeks, after the immunizing step.
29 .- 31 . (canceled)
32 . The method of claim 1 , wherein the isolating step comprises positive selection of B cells and/or negative selection of non-B-cells.
33 .- 34 . (canceled)
35 . The method of claim 1 , wherein the isolating step comprises isolating splenocytes.
36 . The method of claim 1 , wherein the cross-reactive antibody is a cross-neutralizing antibody.
37 .- 59 . (canceled)
60 . The method of claim 1 , wherein the plurality of coronavirus antigens are of coronaviruses in the subgenus of Sarbecovirus.
61 .- 64 . (canceled)
65 . An antibody or fragment thereof derived from a B-cell obtained by the method of claim 1 .
66 . A nucleic acid molecule encoding the antibody or fragment thereof of claim 65 .
67 . An antibody or fragment thereof derived from recombinant expression of the nucleic acid molecule of claim 66 .
68 . (canceled)
69 . A pharmaceutical composition comprising the antibody or fragment thereof of claim 65 .
70 . A method of treating or preventing a disease or disorder caused by a viral infection in a subject in need thereof, comprising: administering to the subject a pharmaceutically effective amount of the pharmaceutical composition of claim 69 , thereby treating or preventing the disease or disorder caused by the viral infection in the subject.
71 .- 81 . (canceled)