Chimeric vaccines
The invention provides chimeric proteins and nucleic acids encoding these which can be used to generate vaccines against selected antigens. In one aspect, a chimeric protein comprises an antigen sequence and a domain for trafficking the protein to an endosomal compartment, irrespective of whether the antigen is derived from a membrane or non-membrane protein. In one preferred aspect, the trafficking domain comprises a lumenal domain of a LAMP polypeptide. Alternatively, or additionally, the chimeric protein comprises a trafficking domain of an endocytic receptor (e.g., such as DEC-205 or gp200-MR6). The vaccines (DNA, RNA or protein) can be used to modulate or enhance an immune response against any kind of antigen. In one preferred aspect, the invention provides a method for treating a patient with cancer by providing a chimeric protein comprising a cancer-specific antigen or a nucleic acid encoding the protein to the patient.
1. A chimeric nucleic acid comprising a vector encoding a fusion protein comprising an antigen domain comprising at least one epitope inserted between two trafficking domains, wherein the two trafficking domains are the luminal domain of a lysosome associated membrane protein and a polypeptide trafficking domain of an endocytic receptor.
2. The chimeric nucleic acid of claim 1 , wherein the antigen domain is fused in frame with the trafficking domains.
3. The chimeric nucleic acid of claim 1 , wherein the trafficking domains direct both membrane and non-membrane proteins to an endosomal or lysosomal compartment in a cell or to a lysosome-related organelle.
4. The chimeric nucleic acid of claim 1 , wherein the lysosome associated membrane protein comprises lysosome associated membrane protein (LAMP)-1, LAMP-2, LAMP-3, DC-LAMP, or lysosomal integral membrane protein (LIMP) polypeptide.
5. A chimeric nucleic acid comprising a vector encoding a fusion protein comprising a Gag polypeptide fused in-frame between two trafficking domains, wherein the two trafficking domains are the luminal domain of a lysosome associated membrane protein and a polypeptide trafficking domain of an endocytic receptor.
6. The chimeric nucleic acid of claim 1 , wherein the antigen domain is an antigen domain from a pathogenic organism.
7. The chimeric nucleic acid of claim 6 , wherein the pathogenic organism is a virus, microorganism, or parasite.
8. The chimeric nucleic acid of claim 7 , wherein the virus is an HIV virus.
9. A composition comprising the chimeric nucleic acid of claim 1 .
10. The composition of claim 9 , wherein the composition further comprises a pharmaceutical carrier.
11. A composition comprising the chimeric nucleic acid of claim 5 .
12. The composition of claim 11 , wherein the composition further comprises a pharmaceutical carrier.
13. A method for modulating an immune response in a subject comprising administering the chimeric DNA of claim 1 to the subject.
14. The method of claim 13 , wherein the subject is a human.
15. A method for modulating an immune response in a subject comprising administering the chimeric DNA of claim 5 to the subject.
16. The method of claim 15 , wherein the subject is a human.