Multivalent live-attenuated influenza vaccine for prevention and control of equine influenza virus (EIV) in horses
The present invention provides compositions and methods related to equine live-attenuated influenza vaccines.
1. A multivalent immunological composition comprising two or more equine live-attenuated influenza viruses (LAIV), comprising:
a first LAIV expressing one or more antigens of a clade 1 H3N8 equine influenza virus; and
a second LAIV expressing one or more antigens of a clade 2 H3N8 equine influenza virus;
wherein each LAIV comprises one or more mutations in one or more of: segment 1 and segment 2 of the viral genome;
wherein the first LAIV expresses HA, NA, or a combination thereof of A/equine/Texas/6/2017 H3N8.
2. The composition of claim 1 , wherein the second LAIV expresses HA, NA, or a combination thereof of A/equine/Richmond/1/2007 H3N8.
3. The composition of claim 1 wherein the segment 1 comprises the nucleic acid sequence set forth in SEQ ID NO: 1.
4. The composition of claim 1 , wherein the segment 2 comprises the nucleic acid sequence set forth in SEQ ID NO: 3.
5. The composition of claim 1 , wherein at least one LAIV comprises one or more mutations in segment 1, which encodes mutant PB2.
6. The composition of claim 5 , wherein mutant PB2 comprises a N265S point mutation, relative to SEQ ID NO: 6.
7. The composition of claim 5 mutant PB2 comprises the amino acid sequence set forth in SEQ ID NO: 2.
8. The composition of claim 1 , wherein at least one LAIV comprises one or more mutations in segment 2, which encodes mutant PB1.
9. The composition of claim 8 , wherein mutant PB1 comprises one or more of: K391E point mutation, relative to SEQ ID NO: 8, E581G point mutation, relative to SEQ ID NO: 8, and A661T point mutation, relative to SEQ ID NO: 8.
10. The composition of claim 8 , wherein mutant PB1 comprises a K391E point mutation, relative to SEQ ID NO: 8, a E581G point mutation, relative to SEQ ID NO: 8, and an A661T point mutation, relative to SEQ ID NO: 8.
11. The composition of claim 8 , wherein mutant PB1 comprises the amino acid sequence set forth in SEQ ID NO: 4.
12. The composition of claim 1 , wherein each LAIV comprises one or more mutations in segment 1, which encodes mutant PB2; and one or more mutations in segment 2, which encodes mutant PB1.
13. The composition of claim 12 , wherein mutant PB2 comprises a N265S point mutation, relative to SEQ ID NO: 6 and wherein mutant PB1 comprises a K391E point mutation, relative to SEQ ID NO: 8, a E581G point mutation, relative to SEQ ID NO: 8, and an A661T point mutation, relative to SEQ ID NO: 8.
14. The composition of claim 1 , wherein the composition is used for the treatment of equine influenza in a subject.
15. The composition of claim 1 , wherein segment 1 of each LAIV is derived from segment 1 of A/equine/Ohio/1/2003; and wherein segment 2 of each LAIV is derived from segment 2 of A/equine/Ohio/1/2003.
16. A method for inducing an immune response against a plurality of equine influenza viruses in a subject, the method comprising administering to the subject the immunological composition of claim 1 .
17. The method of claim 16 , wherein the subject does not have equine influenza, and wherein the method induces immunity against equine influenza.
18. The method of claim 16 , wherein the subject is infected equine influenza, and wherein the method induces a therapeutic immune response.
19. The method of claim 16 , wherein the immunological composition is administered intranasally, intratracheally, orally, intradermally, intramuscularly, intraperitoneally, intravenously, or subcutaneously.
20. The method of claim 16 , wherein the subject is a horse.