Immunogenic compositions and methods of use thereof
Embodiments of the disclosure encompass compositions and methods for generating immune responses in an animal or human host. Embodiments of the compositions encompass proteins derived from the surface proteins of bacteria and protozoa, and in particular the flagellum component flagellin, and which have adjunctival properties when administered in conjunction with an immunogen. Embodiments of the compositions of the disclosure are modified to incorporate a heterologous transmembrane-cytoplasmic domain allowing the peptides to be incorporated into virus-like particles. Embodiments of the methods of generating an immunological response in an animal or human comprise exposing the immune system of an animal or human host to an immunogen and a virus-like particle comprising an adjuvant polypeptide including a host cell Toll-like receptor ligand polypeptide having a transmembrane-cytoplasmic tail polypeptide, and a heterologous signal peptide.
1. The nucleic acid molecule, comprising:
a region encoding a chimeric bacterial flagellin, wherein the chimeric bacterial flagellin has an N-terminal flagellin domain, a C-terminal flagellin domain, a deleted flagellin central variable domain and a heterologous antigenic peptide inserted in the deleted central variable domain such that the antigenic peptide is between the N-, and C-terminal domains of flagellin, wherein the chimeric flagellin is capable of specifically interacting with a Toll-like receptor of an animal or human cell,
a region encoding a heterologous signal peptide; and
a region encoding a transmembrane-cytoplasmic tail capable of being incorporated into a virus-like particle or virosome.
2. The nucleic acid molecule of claim 1 , wherein the heterologous antigenic peptide encodes a viral antigen.
3. The nucleic acid molecule of claim 1 , wherein the heterologous signal peptide is a bee melittin signal peptide.
4. The nucleic acid molecule of claim 1 , comprising:
a first nucleotide sequence encoding an amino acid sequence from amino acid positions of about 1 to about 305 of sequence SEQ ID NO.: 10, or a conservative variant thereof;
a second nucleotide sequence encoding an amino acid sequence from amino acid positions about 430 to about 565 of sequence SEQ ID NO.: 10, or a conservative variant thereof; and
a third nucleotide sequence disposed between the first nucleotide sequence and the second nucleotide sequence, wherein the third nucleotide sequence encodes a heterologous antigenic peptide.
5. The nucleic acid molecule of claim 1 , wherein the nucleic acid molecule is operably inserted into a nucleic acid expression vector.
6. The nucleic acid molecule of claim 5 , wherein the nucleic acid expression vector is selected from the group consisting of: a plasmid, a baculovirus vector, a cosmid, a viral vector, a chromosome, a mini-chromosome, a modified vaccinia Ankara (MVA) vector, a recombinant poxvirus vector, a recombinant adenovirus vector, an alphavirus vector, and a paramyxovirus vector.