Virus-like particles as vaccines for paramyxovirus
AssigneeUniversity of Massachusetts
InventorsTrudy Morrison, Homer D. Pantua
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Abstract
The present invention discloses the method of making and using a novel, non-infective, paramyxovirus vaccine. Paramyxovirus structural proteins within a virus-like particle (VLP) comprise one example of such a vaccine. It is observed that the presence of matrix protein, alone, is sufficient and necessary to provide an effective VLP release. Co-expression of four paramyxovirus structural proteins, however, result in the release of non-infective VLPs with densities and efficiencies of release similar to that of infective particles. Representative diseases wherein a VLP vaccine might be useful include, but are not limited to, Newcastle disease, measles, respiratory syncytial virus infection, and parainfluenza 3 virus infection.
Claims45
A non-infectious, replication incompetent virus-like particle comprising a Newcastle Disease Virus (NDV) matrix protein, wherein said virus-like particle
- i) lacks NDV RNA, and
- ii) is produced by extracellular release from a cell that expresses a recombinant nucleotide sequence comprising a sequence that encodes said Newcastle Disease Virus (NDV) matrix protein,
- wherein at least 85% of the expressed NDV matrix protein is released from said cell.
A non-infectious, replication incompetent virus-like particle comprising a Newcastle Disease Virus (NDV) matrix protein, wherein said virus-like particle
- i) lacks NDV RNA, and
- ii) is produced by extracellular release from a cell that expresses a recombinant nucleotide sequence comprising a sequence that encodes said Newcastle Disease Virus (NDV) matrix protein, and
- wherein at least 85% of the expressed NDV matrix protein is released from said cell, and wherein said NDV matrix protein comprises a Late Domain that functions in extracellular release of said virus-like particles from said cell.
A non-infectious, replication incompetent virus-like particle comprising a Newcastle Disease Virus (NDV) matrix protein, wherein said virus-like particle is produced by extracellular release from a cell that expresses a recombinant nucleotide sequence comprising a sequence that encodes said Newcastle Disease Virus (NDV) matrix protein, wherein at least 85% of the expressed NDV matrix protein is released from said cell, wherein said NDV matrix protein comprises a Late Domain that functions in extracellular release of said virus-like particles from said cell, and wherein said Late Domain comprises an amino acid sequence selected from the group consisting of YPDL (SEQ ID NO:119) and PTAP (SEQ ID NO:4).
A non-infectious, replication incompetent virus-like particle comprising a Newcastle Disease Virus (NDV) matrix protein, wherein said virus-like particle is produced by extracellular release from a cell that expresses a recombinant nucleotide sequence comprising a sequence that encodes said Newcastle Disease Virus (NDV) matrix protein, wherein least 85% of the expressed NDV matrix protein is released from said cell, wherein said NDV matrix protein comprises a Late Domain that functions in extracellular release of said virus-like particles from said cell, wherein said NDV matrix protein comprises a sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:24, and SEQ ID NO:26, except that said amino acid sequence YANL that is at amino acids 232 to 235 of said SEQ ID NO:12, SEQ ID NO:24, and SEQ ID NO:26 is substituted with amino acid sequence PTAP (SEQ ID NO:4).
A non-infectious, replication incompetent virus-like particle comprising a Newcastle Disease Virus (NDV) matrix protein, wherein said virus-like particle is produced by extracellular release from a cell that expresses a recombinant nucleotide sequence comprising a sequence that encodes said Newcastle Disease Virus (NDV) matrix protein, wherein at least 85% of the expressed NDV matrix protein is released from said cell, wherein said NDV matrix protein comprises a Late Domain that functions in extracellular release of said virus-like particles from said cell, wherein said NDV matrix protein comprises a sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:24, and SEQ ID NO:26, except that said amino acid sequence YANL that is at amino acids 232 to 235 of said SEQ ID NO:12, SEQ ID NO:24, and SEQ ID NO:26 is substituted with amino acid sequence YPDL (SEQ ID NO:119).
A non-infectious, replication-incompetent virus-like particle comprising a Newcastle Disease Virus (NDV) matrix protein, wherein said virus-like particle lacks NDV RNA and is produced by extracellular release from a cell that expresses a recombinant nucleotide sequence consisting of a sequence that encodes said Newcastle Disease Virus (NDV) matrix protein.
A non-infectious, replication-incompetent virus-like particle comprising a Newcastle Disease Virus (NDV) matrix protein, wherein said virus-like particle lacks NDV RNA and is produced by extracellular release from a cell that expresses a recombinant nucleotide sequence consisting of a sequence that encodes said Newcastle Disease Virus (NDV) matrix protein, wherein said NDV matrix protein comprises a Late Domain that functions in extracellular release of said virus-like particles from said cell.
A non-infectious, replication-incompetent virus-like particle comprising a Newcastle Disease Virus (NDV) matrix protein, wherein said virus-like particle is produced by extracellular release from a cell that expresses a recombinant nucleotide sequence consisting of a sequence that encodes said Newcastle Disease Virus (NDV) matrix protein, wherein said NDV matrix protein comprises a Late Domain that functions in extracellular release of said virus-like particles from said cell, and wherein said Late Domain comprises an amino acid sequence selected from the group consisting of YPDL (SEQ ID NO:119) and PTAP (SEQ ID NO:4).
A non-infectious, replication-incompetent virus-like particle comprising a Newcastle Disease Virus (NDV) matrix protein, wherein said virus-like particle is produced by extracellular release from a cell that expresses a recombinant nucleotide sequence consisting of a sequence that encodes said Newcastle Disease Virus (NDV) matrix protein, wherein said NDV matrix protein comprises a Late Domain that functions in extracellular release of said virus-like particles from said cell, and wherein said Late Domain comprises amino acid sequence PTAP (SEQ ID NO:4).
A non-infectious, replication-incompetent virus-like particle comprising a Newcastle Disease Virus (NDV) matrix protein, wherein said virus-like particle is produced by extracellular release from a cell that expresses a recombinant nucleotide sequence consisting of a sequence that encodes said Newcastle Disease Virus (NDV) matrix protein, wherein said NDV matrix protein comprises a Late Domain that functions in extracellular release of said virus-like particles from said cell, and wherein said Late Domain comprises amino acid sequence YPDL (SEQ ID NO:119).
Dependencies are inferred from the claim text.