Universal mammalian influenza vaccine
The present invention provides vaccine or immunogenic compositions comprising novel antigens derived from the equine strain of influenza H3N8. These proteins and specific immunogenic domains are effective as primary universal influenza antigens. The disclosed vaccines or immunogenic compositions are highly effective in inducing HA specific antibodies reactive to different influenza viruses, mucosal and systemic immune responses, and cross-protection regardless of influenza virus subtypes. In some embodiments, the vaccine is cross-protective against two or more (e.g., 2, 3, 4, 5, or 6) subtypes of influenza with or without the use of an adjuvant.
1. A cross-protective influenza vaccine comprising an equine H3 antigen or immunogenic fragment thereof, wherein the equine H3 antigen comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 2 and at least one glycosylated residue; and an adjuvant; wherein the vaccine is cross-protective against two or more subtypes of influenza.
2. The vaccine of claim 1 , wherein the equine H3 antigen comprises an amino acid sequence having at least 97% sequence identity to SEQ ID NO: 2.
3. The vaccine of claim 1 , wherein the H3 antigen is on the surface of a virus-like particle (VLP) or in secreted form.
4. The vaccine of claim 1 , wherein the vaccine is a whole inactivated virus, split viral vaccine, or live attenuated influenza vaccine.
5. The vaccine of claim 1 , wherein the vaccine is formulated for delivery via intranasal, intramuscular, subcutaneous, transdermal or sublingual administration.
6. The vaccine of claim 1 , wherein said adjuvant is Alum.
7. A cell comprising an equine H3 antigen or immunogenic fragment thereof, wherein the equine H3 antigen comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 2 and at least one glycosylated residue, and wherein the cell is an insect cell or a yeast cell.
8. A method of vaccinating a subject for influenza comprising administering the cross-protective influenza vaccine of claim 1 to a subject in need thereof by intranasal, intramuscular, subcutaneous, transdermal, or sublingual administration.
9. The method of claim 8 , further comprising administering to the subject a composition comprising an influenza virus-like particle (VLP) vaccine, a whole inactivated virus, split viral vaccine, or live attenuated influenza vaccine.
10. The method of claim 9 , wherein the composition comprising influenza virus-like particle (VLP) vaccine, a whole inactivated virus, split viral vaccine, or live attenuated influenza vaccine is administered before or after the cross-protective influenza vaccine.
11. The method of claim 8 , wherein the cross-protective influenza vaccine is administered prior to influenza seasonal vaccination or after influenza seasonal vaccination.
12. The method of claim 11 , wherein the period between cross-protective influenza vaccine and seasonal vaccination administration is one day to 10 years.
13. A pharmaceutical composition comprising a synthetic or recombinant equine H3 polypeptide comprising multiple copies of a plurality of influenza virus peptide epitopes, wherein the equine H3 polypeptide comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 2 and at least one glycosylated residue, and at least one seasonal or pandemic preparation against influenza, and containing a pharmaceutically acceptable adjuvant.
14. A method for inducing an immune response or conferring protection against influenza in a subject, wherein the method comprises administering to the subject a pharmaceutical composition according to claim 13 .
15. An immunogenic composition comprising an effective amount of a recombinant or synthesized equine H3 antigen or immunogenic fragment thereof, wherein the equine H3 antigen comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 2 and at least one glycosylated residue; an adjuvant; and a pharmaceutically acceptable carrier.
16. A method for generating an immune response to two or more influenza hemagglutinin subtypes and/or influenza types, comprising administering to a subject an effective amount of the immunogenic composition of claim 15 , thereby generating the immune response.
17. The method of claim 16 , wherein said subject is a mammal.
18. The method of claim 16 , wherein said mammal is a human.
19. The method of claim 16 , wherein said mammal is a porcine.