Replication-defective adenoviruses comprising nucleic acids encoding SARS-CoV-2 s glycoprotein and modified N protein comprising an endosomal targeting sequence
Compositions and methods are presented for prevention and/or treatment of a coronavirus disease wherein the composition comprises a recombinant entity. The recombinant entity comprises a nucleic acid that encodes a nucleocapsid protein of coronavirus 2 (CoV2); and/or wherein the recombinant entity encodes a spike protein of CoV2.
1. A nucleic acid comprising a first nucleic acid portion and a second nucleic acid portion; wherein the first nucleic acid portion encodes a CoV2 spike (S) protein having the amino acid sequence of SEQ ID NO:4; and wherein the second nucleic acid portion encodes a chimeric protein comprising 1) a CoV2 nucleocapsid (N) protein having the amino acid sequence of SEQ ID NO: 1 and 2) an endosomal targeting sequence (ETSD) having the amino acid sequence of SEQ ID NO: 2.
2. The nucleic acid of claim 1 , wherein the first nucleic acid portion has a nucleotide sequence of SEQ ID NO:5, and wherein the second nucleic acid portion has a nucleotide sequence of SEQ ID NO:3.
3. The nucleic acid of claim 1 , wherein the nucleic acid further comprises a trafficking sequence for the S protein encoded in the first nucleic acid, a co-stimulatory molecule, and/or an immune stimulatory cytokine.
4. The nucleic acid of claim 3 , wherein the co-stimulatory molecule is selected from the group consisting of CD80, CD86, CD30, CD40, CD30L, CD40L, ICOS-L, B7-H3, B7-H4, CD70, OX40L, 4-IBBL, GITR-L, TIM-3, TIM-4, CD48, CD58, TLIA, ICAM-1, and LFA3.
5. The nucleic acid of claim 3 , wherein the immune stimulatory cytokine is selected from the group consisting of IL-2, IL-12, IL-15, nogapendekin alfa-imbakicept, IL-21, IPSI, and LMPl.
6. A vaccine composition comprising the nucleic acid of claim 1 , wherein the composition is formulated for injection.
7. A method for inducing immunity against CoV2 in a patient in need thereof, the method comprising administering to the patient the vaccine composition of claim 6 .
8. The nucleic acid of claim 1 , wherein the nucleic acid comprises the first and second nucleic acids respectively in a 3′ to 5′ direction.
9. A replication defective adenovirus, wherein the adenovirus comprises:
a. an E1 gene region deletion;
b. an E2b gene region deletion; and
c. the nucleic acid of claim 1 .
10. A yeast or lysate thereof, wherein the yeast comprises the nucleic acid of claim 1 .
11. A replication defective adenoviral vector comprising the following components:
a. an E1 gene region deletion;
b. an E2b gene region deletion;
c. a nucleic acid portion that encodes a SARS-CoV-2 S protein; and
d. a nucleic acid portion that encodes a chimeric protein comprising a SARS-CoV-2 N protein and an endosomal targeting sequence.
12. The replication defective adenoviral vector of claim 11 , wherein the nucleic acid portion that encodes a CoV2 S protein is depicted by SEQ ID NO:5.
13. The replication defective adenoviral vector of claim 11 , wherein the nucleic acid portion that encodes the chimeric protein is depicted by SEQ ID NO:3.
14. The replication defective adenoviral vector of claim 11 , further comprising a trafficking sequence, a co-stimulatory molecule, and/or an immune stimulatory cytokine.
15. The replication defective adenoviral vector of claim 13 , wherein the co-stimulatory molecule is selected from the group consisting of CD80, CD86, CD30, CD40, CD30L, CD40L, ICOS-L, B7-H3, B7-H4, CD70, OX40L, 4-IBBL, GITR-L, TIM-3, TIM-4, CD48, CD58, TLIA, ICAM-1, and LFA3.
16. The replication defective adenoviral vector of claim 13 , wherein the immune stimulatory cytokine is selected from the group consisting of IL-2, IL-12, IL-15, nogapendekin alfa-imbakicept, IL-21, IPSI, and LMPl.