SARS-COV-2 VACCINE COMPOSITIONS
Disclosed herein are coronavirus (CoV) Spike(S) polypeptides, including naturally and non-naturally occurring polypeptides, and nanoparticles and immunogenic compositions comprising the same, which are useful for stimulating immune responses against various SARS-COV-2 strains. The nanoparticles present antigens from pathogens surrounded to and associated with a detergent core resulting in enhanced stability and good immunogenicity. Dosages, formulations, and methods for preparing the vaccines and nanoparticles are also disclosed.
1 . An immunogenic composition comprising a first CoV S glycoprotein having an amino acid sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to any of SEQ ID NOS: 329.
2 . The immunogenic composition of claim 1 , comprising from 0.1 μg to 25 μg, 0.1 μg to 10 μg, 0.001 μg to 10 μg, 0.001 μg to 25 μg, or from 0.1 μg to 5 μg of the first CoV S glycoprotoein.
3 . The immunogenic composition of claim 1 , comprising a nanoparticle comprising the first CoV S glycoprotein and a non-ionic detergent core.
4 . The immunogenic composition of claim 3 , wherein the non-ionic detergent is selected from the group consisting of polysorbate-20 (PS20), polysorbate-40 (PS40), polysorbate-60 (PS60), polysorbate-65 (PS65), and polysorbate-80 (PS80).
5 . The immunogenic composition of claim 1 , further comprising an adjuvant and a pharmaceutically acceptable carrier.
6 . The immunogenic composition of claim 5 , wherein the adjuvant is a saponin adjuvant.
7 . The immunogenic composition of claim 6 , wherein the saponin adjuvant comprises at least two iscom particles, wherein:
the first iscom particle comprises fraction A of Quillaja Saponaria Molina and not fraction C of Quillaja Saponaria Molina; and
the second iscom particle comprises fraction C of Quillaja Saponaria Molina and not fraction A of Quillaja Saponaria Molina.
8 . The immunogenic composition of claim 5 , comprising from about 25 μg to about 100 μg of adjuvant.
9 . The immunogenic composition of claim 1 , wherein the immunogenic composition is contained in a syringe.
10 . A method of stimulating an immune response against SARS-COV-2 or a heterogeneous SARS-COV-2 strain thereof in a human comprising administering the immunogenic composition of claim 1 to the human.
11 . A method of boosting an immune response against SARS-COV-2 or a heterogeneous SARS-COV-2 strain thereof in a human comprising administering:
a first immunogenic composition comprising (a) one or more first SARS-COV-2 S glycoproteins having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to SEQ ID NO: 329, and (b) a pharmaceutically acceptable buffer;
wherein the immunogenic composition is administered after administration of another immunogenic composition intended to produce an immunogenic response against SARS-CoV-2 or a heterogeneous SARS-COV-2 strain thereof in the human.
12 . The method of claim 11 , comprising administering a first dose of the first immunogenic composition at least 21 days after administration of the other immunogenic composition.
13 . The method of claim 12 , comprising administering the first immunogenic composition from about 1 month to about 18 months, from about 6 months to about 18 months, from about 9 months to about 18 months, from about 12 months to about 15 months, or from about 12 months to about 18 months after administration of the other immunogenic composition.
14 . The method of claim 11 , wherein the other immunogenic composition comprises an mRNA vaccine or a protein subunit vaccine.
15 . The method of claim 14 , wherein the protein subunit vaccine of the other immunogenic composition comprises at least one or more second SARS-COV-2 S glycoproteins having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to any of SEQ ID NOS: 87, 260, 222, 227, 274, and 284, and 329.
16 . The immunogenic composition of claim 1 , wherein the first CoV S glycoprotein comprises one or more modifications compared to SEQ ID NO: 329 at amino acid 59,346,456, 475, 572, and 1087, wherein the one or more modifications are numbered according to SEQ ID NO: 1.
17 . The immunogenic composition of claim 16 , wherein:
(i) amino acid at 59 is phenylalanine or serine;
(ii) amino acid at 346 is arginine or threonine;
(iii) amino acid at 456 is phenylalanine or leucine;
(iv) amino acid at 475 is alanine or valine:
(v) amino acid at 572 is threonine or isoleucine; and
(vi) amino acid at 1087 is alanine or serine.
18 . A method of inducing an immune response against SARS-COV-2 or a heterogeneous SARS-COV-2 strain thereof in a human comprising administering:
a first immunogenic composition comprising (a) one or more first SARS-COV-2 S glycoproteins having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to SEQ ID NO: 329, and (b) a pharmaceutically acceptable buffer.
19 . A method as recited in claim 18 , further comprising administering a second immunogenic composition, comprising (a) one or more second SARS-COV-2 S glycoproteins having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to any of SEQ ID NOS: 87, 260, 222, 227, 274, and 284, and 329.
20 . An immunogenic composition comprising:
(i) one or more non-naturally occurring SARS-COV-2 S glycoproteins having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to any one of SEQ ID NOS: 87, 260, 222, 227, 274, and 284; and
(ii) a pharmaceutically acceptable buffer.