Coronavirus vaccine comprising a mosaic protein
Disclosed herein are mosaic coronavirus (MoCoV) spike(S) proteins or antigenic fragments thereof. Also disclosed herein are nucleic acid constructs comprising one or more nucleic acid sequences encoding a MoCoV S protein or antigenic fragment thereof. Also disclosed herein are coronavirus vaccine vectors comprising one or more polynucleotides encoding a MoCoV S protein or antigenic fragment thereof. Also disclosed herein are coronavirus vaccines comprising one or more MoCoV S proteins or antigenic fragments thereof and one or more carriers. Also disclosed herein are pharmaceutical compositions, host cells, and kits comprising one or more of the MoCoV S proteins or antigenic fragments thereof, nucleic acid constructs, coronavirus vaccine vectors, and/or coronavirus vaccines. Also disclosed herein are methods of eliciting an immune response in a subject against one or more coronavirus antigens and methods of preventing, reducing the incidence of, attenuating, or treating coronavirus infection in a subject in need thereof.
1 . A nucleic acid construct comprising one or more nucleic acid sequences selected from the group consisting of:
(i) a first nucleic acid sequence encoding a first mosaic coronavirus (MoCoV) spike(S) protein or an antigenic fragment thereof;
(ii) a first nucleic acid sequence encoding a first MoCOV S protein or an antigenic fragment thereof and a second nucleic acid sequence encoding a second MoCoV S protein or an antigenic fragment thereof,
(iii) a first nucleic acid sequence encoding a first MoCoV S protein or an antigenic fragment thereof, a second nucleic acid sequence encoding a second MoCoV S protein or an antigenic fragment thereof, and a third nucleic acid sequence encoding a third MoCoV S protein or an antigenic fragment thereof; and
(iv) combinations thereof,
wherein:
(a) the first nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 10;
(b) the first nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 10, and the second nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 14; or
(c) the first nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 10, the second nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 14, and the third nucleic acid sequence comprises the nucleic acid sequence of SEQ ID NO: 6.
2 . The nucleic acid construct of claim 1 , wherein the first MoCOV S protein or antigenic fragment thereof comprises the amino acid sequence of SEQ ID NO: 9.
3 . The nucleic acid construct of claim 1 , wherein the nucleic acid construct further comprises one or more promoters.
4 . A pharmaceutical composition comprising the nucleic acid construct of claim 1 and one or more carriers that render the composition suitable for pharmaceutical use.
5 . A host cell comprising the nucleic acid construct of claim 1 , wherein the host cell is a cell line.
6 . A coronavirus vaccine vector comprising a first polynucleotide encoding a first MoCoV S protein or an antigenic fragment thereof corresponding to SEQ ID NO: 9.
7 . The coronavirus vaccine vector of claim 6 , wherein the coronavirus vaccine vector further comprises a second polynucleotide encoding a second MoCoV S protein or an antigenic fragment thereof, wherein second MoCoV S protein or antigenic fragment thereof comprises the amino acid sequence of SEQ ID NO: 3 or SEQ ID NO: 13.
8 . The coronavirus vaccine vector of claim 7 , wherein the coronavirus vaccine vector further comprises a third polynucleotide encoding a third MoCoV S protein or an antigenic fragment thereof, wherein third MoCoV S protein or antigenic fragment thereof comprises the amino acid sequence of SEQ ID NO: 5.
9 . The coronavirus vaccine vector of claim 6 , wherein the first polynucleotide comprises the nucleic acid sequence of SEQ ID NO: 10.
10 . The coronavirus vaccine vector of claim 6 , wherein the coronavirus vaccine vector further comprises one or more promoters.
11 . The coronavirus vaccine vector of claim 6 , wherein the coronavirus vaccine vector is a poxvirus vector, a vaccinia virus vector, or a modified vaccinia Ankara (MVA) vector.
12 . A coronavirus vaccine comprising a first MoCoV S protein or an antigenic fragment thereof comprising the amino acid sequence of SEQ ID NO: 9, a second MoCOV S protein or an antigenic fragment thereof comprising the amino acid sequence of SEQ ID NO: 13, and one or more carriers.
13 . The coronavirus vaccine of claim 12 , wherein the coronavirus vaccine further comprises a third MoCoV S protein or an antigenic fragment thereof comprising the amino acid sequence of SEQ ID NO: 5.
14 . A kit comprising the nucleic acid construct of claim 1 .
15 . A method of eliciting an immune response in a subject against one or more coronavirus antigens, the method comprising administering the coronavirus vaccine of claim 12 to the subject, wherein the coronavirus vaccine is effective to elicit an immune response in the subject to the one or more coronavirus antigens.
16 . The method of claim 15 , wherein the one or more doses of the pharmaceutical composition, the coronavirus vaccine vector, or the coronavirus vaccine are effective to elicit an immune response in the subject to coronavirus antigens from at least two different coronavirus strains, wherein the coronavirus strains are selected from the group consisting of: a newly emergent coronavirus strain, HCoV-OC43, SARS-COV, MERS-COV, SARS-COV-2, HCOV-229E, HCoV-NL63, BtCoV-HKU4, BtCoV-HKU5, BtCoV-HKU9, BtCoV-273, BtCoV-HKU3, and BtCoV-279.
17 . The method of claim 15 , wherein the one or more doses of the pharmaceutical composition, the coronavirus vaccine vector, or the coronavirus vaccine are administered to the subject by a buccal, epidermal, epidural, intraarterial, intraarticular, intracapsular, intracardiac, intracoronary, intradermal, intralesional, intralymphatic, intramuscular, intranasal, intraorbital, intraperitoneal, intraspinal, intrasterna, intrathecal, intravenous, mucosal, oral, rectal, subarachnoid, subcapsular, subcutaneous, subcuticular, sublingual, topical, transtracheal, or vaginal route of administration or any combination thereof.
18 . A composition comprising a lipid nanoparticle and a messenger RNA (mRNA) comprising an open reading frame (ORF) that comprises a first nucleotide sequence, wherein the first nucleotide sequence encodes a first polypeptide comprising the amino acid sequence of SEQ ID NO: 9.
19 . The composition of claim 18 , wherein the first nucleotide sequence comprises the nucleotide sequence SEQ ID NO: 10.
20 . The composition of claim 18 , wherein the mRNA further comprises a second nucleotide sequence that encodes a second polypeptide comprising the amino acid sequence of SEQ ID NO: 13.
21 . The composition of claim 20 , wherein the second nucleotide sequence comprises the nucleotide sequence of SEQ ID NO: 14.
22 . The composition of claim 20 , wherein the mRNA further comprises a third nucleotide sequence that encodes a third polypeptide comprising the amino acid sequence of SEQ ID NO: 5.
23 . The composition of claim 22 , wherein the third nucleotide sequence comprises the nucleotide sequence of SEQ ID NO: 6.
24 . The composition of claim 18 , wherein the lipid nanoparticle comprises a PEG-modified lipid, a non-cationic lipid, a sterol, an ionizable cationic lipid, or any combination thereof.