Nucleic acid respiratory syncytial virus vaccines

• US 6,486,135 B1
• Filed: 05/12/2000
• Issued: 11/26/2002
• Est. Priority Date: 06/07/1995
• Status: Expired due to Fees

• Current Assignee: Aventis Pasteur Limited (Sanofi )
• Original Assignee: Aventis Pasteur Limited (Sanofi )
• Inventors: Ewasyshyn, Mary E., Sambhara, Suryaprakash, Klein, Michel H., Li, Xiaomao
• Primary Examiner(s): Yucel, Remy
• Assistant Examiner(s): LOEB, BRONWEN
• Application Number:
  US09/570,383
• Time in Patent Office: 928 Days
• Field of Search: 514/44, 435/69.1, 435/69.3, 435/91.4, 424/211.1
• US Class Current: 514/44.00R
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 2319/02 containing a signal sequence
• CPC Class Codes: C12N 15/85 for animal cells
• CPC Class Codes: C12N 2760/18522 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2800/108 episomal vectors
• CPC Class Codes: C12N 2830/42 being an intron or intervening sequence for splicing and/or stability of RNA
• CPC Class Codes: C12N 2840/20 translation of more than one cistron

Abstract

Non-replicating vectors containing a nucleotide sequence coding for an F protein of respiratory syncytial virus (RSV) and a promoter for such sequence, preferably a cytomegalovirus promoter, are described for in vivo immunization. The nucleotide sequence encloding the RSV F protein may lack a sequence encoding the homologous signal peptide but possessing a heterologous signal peptide enhancing RSV F protein expression. Such non-replicating vectors, including plasmids, also may contain a further nucleotide sequence located adjacent to the RSV F protein encoding sequence to enhance the immunoprotective ability of the RSV F protein when expressed in vivo. Such non-replicating vectors may be used to immunize a host against disease caused by infection with RSV, including a human host, by administration thereto, and may be formulated as immunogenic compositions with pharmaceutically-acceptable carriers for such purpose. Such vectors also may be used to produce antibodies for detection of RSV infection in a sample.

Claims

1. A method of using a gene encoding an RSV F protein lacking the transmembrane region to produce an immune response in a host, which comprises:

isolating said gene;

operatively linking said gene to at least one control sequence to produce a plasmid vector, said control sequence directing expression of said RSV F protein when said vector is introduced into a host to produce an immune response to said RSV F protein; and

introducing said vector into the host.

2. The method of claim 1 wherein said at least one control sequence comprises the immediate early cytomegalovirus promoter.

3. The method of claims 1 wherein said gene encoding an RSV F protein encodes an RSV F protein fragment lacking an autologous RSV F signal peptide sequence and includes a sequence encoding a heterologous signal peptide which enhance the level of expression of RSV F protein.

4. The method of claims 3 wherein said gene coding an RSV F protein encoding a signal peptide encodes HSV I gD.

5. The method of claim 4 wherein said at least one control sequence comprises the immediately early cytomegalovirus promoter.

6. The method of claim 5 including the step of:

operatively linking said gene to an immunoprotective enhancing sequence which comprises a pair of splice sites to prevent aberrant mRNA splicing to produce an enhanced immunoprotection to said RSV F protein in said host.

7. The method of claim 6 wherein said immunoprotection enhancing sequence is that of rabbit β

-globin intron II.