Attenuated bovine coronavirus and related vaccines
The present invention discloses novel attenuated bovine coronavirus isolates, compositions comprising these isolate, and methods of using such compositions in vaccines, including in live vaccines. The present invention further discloses the administration of such vaccines, including the intranasal administration of such vaccines, to aid in the prevention of respiratory disease caused by bovine coronavirus.
1. An attenuated bovine coronavirus (BCoV) that comprises a genome that encodes a spike protein that has greater than 99% identity with the amino acid sequence of SEQ ID NO: 2;
a hemagglutinin-esterase glycoprotein (HE) that has 98% or greater identity with the amino acid sequence of SEQ ID NO: 4;
an integral membrane protein (M) that has 98% or greater identity with the amino acid sequence of SEQ ID NO: 6; and
a nucleocapsid protein (N) that has 98% or greater identity with the amino acid sequence of SEQ ID NO: 10.
2. The attenuated bovine coronavirus (BCoV) of claim 1 that comprises a nucleotide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 9, SEQ ID NO: 11, and any combination thereof.
3. The BCoV of claim 1 that further encodes one or more of following proteins selected from the group consisting of:
an Orf 1 ab protein that has 98% or greater identity with the amino acid sequence of SEQ ID NO: 12, an Orf 2a protein that has 98% or greater identity with the amino acid sequence of SEQ ID NO: 14, and a 4.9 kDa protein that has 98% or greater identity with the amino acid sequence of SEQ ID NO: 16.
4. The BCoV of claim 1 that further encodes a small membrane protein (E) that has 98% or greater identity with the amino acid sequence of SEQ ID NO: 8.
5. The BCoV of claim 2 that further comprises the nucleotide sequence of SEQ ID NO: 7.
6. An attenuated bovine coronavirus (BCoV) comprising the immunogenic properties of the bovine coronavirus having the ATCC deposit number PTA-121515 or is the progeny of said BCoV.
7. A vaccine comprising the BCoV of claim 1 .
8. The vaccine of claim 7 , wherein the attenuated BCoV is live.
9. The vaccine of claim 8 that is stored as a liquid stable vaccine.
10. The vaccine of claim 7 further comprising one or more additional viruses selected from the group consisting of a bovine viral diarrhea virus (BVDV), infectious bovine rinotracheitis virus (IBR), parainfluenza type 3 virus (PI3), bovine respiratory syncytial virus (BRSV), Rift Valley fever virus (RVFV), and any combination thereof.
11. The vaccine of claim 7 further comprising one or more bacteria selected from the group consisting of a Pasteurella multocida , a Mannheimia haemolytica , a Histophilus somni , a Mycoplasma bovis , and any combination thereof.
12. The vaccine of claim 11 wherein said one or more bacteria are live attenuated bacteria.
13. A method of vaccinating a bovine comprising administering the vaccine of claim 7 .
14. The method of claim 13 wherein said administering is performed intranasally.
15. The attenuated (BCoV) of claim 1 that comprises a genome that encodes a spike protein that comprises the amino acid sequence of SEQ ID NO: 2;
a hemagglutinin-esterase glycoprotein (HE) that comprises the amino acid sequence of SEQ ID NO: 4;
an integral membrane protein (M) that comprises the amino acid sequence of SEQ ID NO: 6; and
a nucleocapsid protein (N) that comprises the amino acid sequence of SEQ ID NO: 10.
16. The BCoV of claim 15 that further encodes one or more of following proteins selected from the group consisting of:
an Orf 1 ab protein that has 98% or greater identity with the amino acid sequence of SEQ ID NO: 12, an Orf 2a protein that has 98% or greater identity with the amino acid sequence of SEQ ID NO: 14, and a 4.9 kDa protein that has 98% or greater identity with the amino acid sequence of SEQ ID NO: 16.
17. A vaccine comprising the BCoV of claim 16 .
18. An attenuated bovine coronavirus (BCoV) having the ATCC deposit number PTA-121515.
19. A vaccine comprising the BCoV of claim 18 .
20. The vaccine of claim 19 , wherein the attenuated BCoV is live.