COMPOSITIONS AND METHODS THAT ENHANCE AN IMMUNE RESPONSE
Disclosed herein are isolated nucleic acids, compositions of isolated nucleic acids, and compositions of polypeptides that are useful for the generation, enhancement, or improvement of an immune response to a target antigen. Some embodiments of the compositions include hepatitis B core antigen (HBcAg) protein and a heterologous protein antigen. In some embodiments, an isolated nucleic acid encoding hepatitis B core antigen (HBcAg) protein and a heterologous protein antigen is disclosed. Also disclosed herein are methods of administering the composition or isolated nucleic acid to generate an immune response, where HBcAg acts as adjuvant to improve the immune response to the heterologous protein. In certain embodiments, the HBcAg is as a stork or heron hepatitis antigen.
1 . An expression construct comprising an isolated nucleic acid that comprises:
a nucleotide sequence encoding a fusion protein of a hepatitis B virus core antigen (HBcAg) from an avian hepatitis virus joined to a hepatitis C virus (HCV) antigen, wherein said HCV antigen comprises NS3/4A and, wherein said nucleotide sequence is codon optimized for expression in humans.
2 . The expression construct of claim 1 , wherein said HCV antigen further comprises NS5A.
3 . The expression construct of claim 1 , wherein one or more protein cleavage sites are encoded between the HBcAg portion and the NS3/4A antigen portion of said fusion protein.
4 . The expression construct of claim 3 , wherein said one or more protein cleavage sites are included at a non-naturally occurring position with respect to the HBcAg.
5 . The expression construct of claim 3 , wherein said one or more protein cleavage sites are NS3 protease cleavage sites.
6 . The expression construct of claim 1 , wherein said HBcAg is from a hepatitis virus that infects a stork.
7 . The expression construct of claim 1 , wherein said HBcAg is from a hepatitis virus that infects a heron.
8 . An immunogenic composition comprising:
an isolated nucleic acid that comprises a nucleotide sequence encoding a fusion protein of a hepatitis B virus core antigen (HBcAg) from an avian hepatitis virus joined to a hepatitis C virus (HCV) antigen, wherein said nucleotide sequence is codon optimized for expression in humans and said HCV antigen comprises NS3/4A; and
an excipient.
9 . The immunogenic composition of claim 8 , further comprising an adjuvant.
10 . The immunogenic composition of claim 9 , wherein said adjuvant is selected from the group consisting of: interleukin 2 (IL-2), interleukin 12 (IL-12), interleukin 15 (IL-15), and interleukin 21 (IL-21).
11 . The immunogenic composition of claim 8 , wherein said HCV antigen further comprises NS5A.
12 . The immunogenic composition of claim 8 , wherein one or more protein cleavage sites are encoded between the HBcAg portion and the NS3/4A antigen portion of said fusion protein.
13 . The immunogenic composition of claim 8 , wherein said one or more protein cleavage sites are included at a non-naturally occurring position with respect to the HBcAg.
14 . The immunogenic composition of claim 8 , wherein said one or more protein cleavage sites are NS3 protease cleavage sites.
15 . The immunogenic composition of claim 8 , wherein said HBcAg is from a hepatitis virus that infects a stork.
16 . The immunogenic composition of claim 8 , wherein said HBcAg is from a hepatitis virus that infects a heron.
17 . A method of inducing an immune response to a hepatitis C virus (HCV) antigen in a subject comprising:
providing the expression construct of claim 1 to a subject; and
evaluating the immune response of said subject to said HCV antigen.
18 . The method of claim 17 , wherein the subject is infected with hepatitis B virus (HBV) or the subject that has antibodies specific for HBV.
19 . The method of claim 17 , wherein said subject is chronically infected with HCV.
20 . A method of inducing an immune response to a hepatitis C virus (HCV) antigen in a subject comprising:
providing the immunogenic composition of claim 8 to a subject; and
evaluating the immune response of said subject to said HCV antigen.
21 . The method of claim 20 , wherein the subject is infected with hepatitis B virus (HBV) or the subject that has antibodies specific for HBV.
22 . The method of claim 20 , wherein said subject is chronically infected with HCV.