Large and small T antigens of merkel cell polyomavirus, nucleic acid constructs and vaccines made therefrom, and methods of using same
AssigneeThe Wistar Institute of Anatomy and Biology
InventorsDavid B. Weiner, Elizabeth Duperret
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Abstract
Nucleic acid molecules and compositions comprising one or more nucleotide sequences that encode a consensus Merkel Cell Polyomavirus (MCV) T antigen. Immunomodulatory methods and methods of inducing an immune response against MCV are disclosed. Method of treating infection by MCV and methods of treating or preventing Merkel Cell Carcinoma associated with MCV are disclosed. Modified consensus MCV T antigens are disclosed.
Claims18
A nucleic acid molecule encoding at least one modified Merkel Cell Polyomavirus (MCV) T antigen, wherein the T antigen comprises at least one mutation that disrupts at least one oncogenic feature of a native MCV T antigen selected from the group consisting of CR1 binding, DnaJ binding, phophatase pp2A binding, Rb binding, ATPase activity, helicase activity, chaperone protein binding, hVam6p binding, Fbxw7 binding, origin binding, and transformation;
- wherein the nucleic acid molecule comprises a sequence selected from the group consisting of:
- a) a nucleotide sequence encoding an amino acid sequence comprising at least 98% identity to SEQ ID NO:4;
- b) a nucleotide sequence encoding an amino acid sequence comprising at least 90% identity to SEQ ID NO:6;
- c) a nucleotide sequence encoding an amino acid sequence selected from the group consisting of SEQ ID NO:4 and SEQ ID NO:6;
- d) a nucleotide sequence having at least about 90% identity over an entire length of a nucleotide sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3 and SEQ ID NO:5;
- and
- e) a nucleotide sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3 and SEQ ID NO:5.
A peptide comprising an amino acid sequence selected from the group consisting of
- a) an amino acid sequence comprising at least 98% identity to SEQ ID NO:4;
- b) an amino acid sequence comprising at least 90% identity to SEQ ID NO:6;
- and
- c) an amino acid sequence selected from the group consisting of SEQ ID NO:4 and SEQ ID NO:6.
Dependencies are inferred from the claim text.