Composite antigenic sequences and vaccines
The invention relates to composite antigens comprising a peptide with contiguous amino acid sequence derived from a plurality of antigenic epitopes of one or more pathogens that induces an immune response in a mammal that is protective against infection by the one or more pathogens. In addition, the invention relates to vaccines comprising composite antigens and to method for treating and preventing an infection.
1. A composite antigen, wherein said antigen is a sequence derived from two antigenic epitopes,
wherein said two epitopes comprise similar sequences at the N- and C-terminal portions of the epitope but comprise different amino acid sequences in the middle of said epitope, and wherein said two epitopes are from one or more pathogens,
wherein said composite antigen comprises the formula A1 BCA2, wherein:
1) A1 is the consensus sequence between the two epitopes that are the common amino acids at the N-terminus of each epitope, and wherein A1 is less than 30 amino acids;
2) B represents the one or two middle amino acid residue(s) from the first epitope that differ from the second epitope;
3) C represents the one or two middle amino acid residue(s) from the second epitope that differ from the first epitope;
4) A2 is the consensus sequence between the two epitopes that are the common amino acids at the C-terminus of each epitope, and wherein A2 is less than 30 amino acids;
wherein said resulting composite antigen induces an immune response in a mammal against the one or more pathogens.
2. The composite antigen of claim 1 , wherein the two antigenic epitopes are composite epitopes.
3. The composite antigen of claim 1 , wherein the amino acids of the composite antigen sequence are natural amino acids.
4. The composite antigen of claim 1 , wherein said antigen is linked to one or more additional epitopes, one or more additional composite epitopes, or a combination thereof.
5. The composite antigen of claim 1 , wherein the amino acid sequence of at least one epitope does not exist naturally.
6. The composite antigen of claim 1 , wherein the one or more pathogens are viruses, bacteria, parasites, yeast, fungi, or a combination thereof.
7. The composite antigen of claim 1 , wherein the one or more pathogens are influenza virus and the antigenic epitopes are from M1, M2, HA, NA, PB1, or PB2 proteins, or a combination thereof.
8. The composite antigen of claim 7 , wherein the two different antigenic epitopes comprise SEQ ID NOs 4 and 5, or SEQ ID NOs 19 and 20, or SEQ ID NOs 52 and 53, or SEQ ID NOs 56 and 57, or SEQ ID NOs 80 and 81, or SEQ ID NOs 83 and 84.
9. The composite antigen of claim 1 , which comprises SEQ ID NOs: 6, 7, 21, 22, 54, 55, 58, 59, 82, 85, or 86.
10. A recombinant polynucleotide that encodes the composite antigen of claim 1 .
11. A vaccine composition comprising the composite antigen of claim 1 .
12. A DNA vaccine that encodes the composite antigen of claim 1 .
13. The composite antigen of claim 1 , wherein the different epitopes are derived from different serotypes of a same pathogen.
14. The composite antigen of claim 1 , wherein the one or more pathogen is influenza virus.