Recombinant measles viruses expressing epitopes of antigens of RNA viruses—use for the preparation of vaccine compositions
AssigneesInstitut Pasteur, Centre National De La Recherche Scientifique
InventorsFrédéric Tangy, Clarisse Lorin, Lucile Mollet, Frédéric Delebecque
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Abstract
The invention relates to a recombinant measles virus expressing a heterologous amino acid sequence derived from an antigen of a determined RNA virus, the recombinant measles virus being capable of eliciting a humoral and/or cellular immune response against measles virus or against the RNA virus or against both measles virus and against the RNA virus. It also relates to the use of the recombinant measles virus for the preparation of immunogenic compositions.
Claims19
An expression vector for producing an infectious recombinant Schwarz strain of measles virus comprising:
- A) the nucleotide sequence encoding the full length antigenomic (+)RNA strand of the measles virus Schwarz strain (from position 83 to position 15976 of SEQ ID NO:
- 16);
- B) a T7 promoter sequence comprising a GGG motif at its 3′ end, operably linked to the nucleotide sequence of A;
- C) a hammerhead ribozyme sequence (from position 29 to position 82 of SEQ ID NO:
- 16) located adjacent to the GGG motif at one end and adjacent to the first nucleotide of the nucleotide sequence encoding the full length anti-genomic (+)RNA strand of the measles virus Schwarz strain at the other end;
- D) a T7 terminator sequence operably linked to the nucleotide sequence of A;
- E) the sequence of a hepatitis delta virus ribozyme located adjacent to the last nucleotide of the nucleotide sequence encoding the full length anti-genomic (+)RNA strand of the measles virus Schwarz strain;
- and
- F) a heterologous coding sequence encoding a heterologous amino acid sequence comprising an antigen of a heterologous RNA virus selected from a retrovirus and a flavivirus.
An infectious recombinant Schwarz strain of measles virus comprising a heterologous coding sequence encoding a heterologous amino acid sequence, wherein the heterologous amino acid sequence is selected from the group consisting of:
- A) gp160ΔV3 (SEQ ID NO:
- 31), in which the V3 loop consisting of amino acids 299 to 334 of SEQ ID NO:
- 27 is replaced by the sequence AAELDKWASAA (SEQ ID NO:
- 8);
- B) gp160ΔV1V2 (SEQ ID NO:
- 35), in which the V1 and V2 loops consisting of amino acids 131 to 159 and 164 to 198 of SEQ ID NO:
- 27, respectively, are deleted;
- C) gp160ΔV1V2V3 (SEQ ID NO:
- 39) in which the V1 and V2 loops consisting of amino acids 131 to 159 and 164 to 198 of SEQ ID NO:
- 27, respectively, are deleted and the V3 loop consisting of amino acids 299 to 334 (SEQ ID NO:
- 27) is replaced by the sequence AAELDKWASAA (SEQ ID NO:
- 8);
- D) gp140ΔV3 (SEQ ID NO:
- 29) in which the V3 loop consisting of amino acids 299 to 334 of SEQ ID NO:
- 25 is replaced by the sequence AAELDKWASAA (SEQ ID NO:
- 8);
- E) gp140ΔV1V2 (SEQ ID NO:
- 33) in which the V1 and V2 loops consisting of amino acids 131 to 159 and 164 to 198 of SEQ ID NO:
- 25, respectively, are deleted;
- and
- F) gp140ΔV1V2V3 (SEQ ID NO:
- 37) in which the V1 and V2 loops consisting of amino acids 131 to 159 and 164 to 198 of SEQ ID NO:
- 25, respectively, are deleted and the V3 loop consisting of amino acids 299 to 334 of SEQ ID NO:
- 25 is replaced by the sequence AAELDKWASAA (SEQ ID NO:
- 8);
- and
- wherein the recombinant virus is infectious in Vero cells and CEF cells.
A recombinant vector selected from the following vectors deposited with the COLLECTION NATIONALE DE CULTURES DE MICROORGANISMES (CNCM):
- pTM-MVSchw2-GFPbis-
- CNCM I-3034,
- pTM-MVSchw2-p17p24[delta]myr(HIVB)
- CNCM I-3035,
- pTM-MVSchw3-Tat(HIV89-6p)
- CNCM I-3036,
- pTM-MVschw3-GFP
- CNCM I-3037,
- pTM-MVSchw2-Es (YFV)
- CNCM I-3038,
- pTM-MVSchw2-gp140 [delta] V1 V2 V3(HIV89-6)
- CNCM I-3054,
- pTM-MVSchw2-gp140 [delta] V3(HIV89-6)
- CNMC I-3055,
- pTM-MVSchw2-gp160 [delta] V1 V2 V3(HIV89-6)
- CNCM I-3056, and
- pTM-MVSchw2-gpl 60 [delta] V1 V2(HIV89-6)
- CNCM I-3057.
Dependencies are inferred from the claim text.