Codon modified immunogenic compositions and methods of use

• US 8,772,256 B2
• Filed: 11/30/2007
• Issued: 07/08/2014
• Est. Priority Date: 11/30/2006
• Status: Active Grant

• Current Assignee: Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services, United States Department Of Health And Human Services
• Original Assignee: United States Department Of Health And Human Services
• Inventors: Graham, Barney S., Johnson, Teresa R.
• Primary Examiner(s): WEHBE, ANNE MARIE SABRINA
• Application Number:
  US12/517,194
• Publication Number:
  US 20100247621A1
• Time in Patent Office: 2,412 Days
• Field of Search: 514/44.R, 435/320.1, 435/325, 536/23.72, 424/199.1
• US Class Current: 514/44.R
• CPC Class Codes: A61K 2039/5256 expressing foreign proteins
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/155 Paramyxoviridae, e.g. parainfluenza virus
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C12N 2710/10343 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2710/24143 viral genome or elements thereof as genetic vector
• 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 2760/18534 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2770/36143 viral genome or elements thereof as genetic vector

Abstract

The present invention features immunogenic compositions comprising codon modified genes that encode viral proteins and/or glycoproteins or fragments. The immunogenic compositions of the invention are useful in various methods of treatment, such as preventing or treating viral infection. Also provided in the present invention are kits and instructions for use.

Claims

1. An immunogenic composition for eliciting a CD8+ T cell and antibody response comprising a codon-modified gene encoding a Respiratory Syncytial Virus (RSV) F protein, wherein the codon-modified F gene comprises SEQ ID NO:

14, 17, or 18.

2. The immunogenic composition according to claim 1, wherein the codon-modified gene induces an immune response.

3. The immunogenic composition of claim 2, wherein the immune response is a T cell response.

4. The immunogenic composition of claim 1, wherein the codon-modified gene comprises one or more mutations.

5. The immunogenic composition of claim 1, wherein the codon-modified F gene comprises SEQ ID NO:

17 or 18.

6. A kit for use in eliciting an immune response capable of preventing an RSV infection in a subject, the kit comprising:

the immunogenic composition of claim 1; and

a pharmaceutically acceptable carrier.

15. A method of eliciting a CD8+ T cell and antibody response capable of preventing an RSV infection in a subject comprising

administering to the subject the immunogenic composition of claim 1 and a pharmaceutically acceptable carrier.

16. The method of claim 15, wherein the immunogenic composition is administered in a prime boost regimen.

17. The method of claim 16, wherein the prime boost regimen increases T cell cytolytic function.

7. A nucleic acid molecule comprising a codon-modified gene encoding a Respiratory Syncytial Virus (RSV) F protein, wherein said gene comprises SEQ ID NO:

14, 17, or 18.

8. A vector comprising a nucleic acid molecule selected from the group consisting of SEQ ID NO:

14, 17, and 18.

9. The vector of claim 8, wherein the nucleic acid molecule is a codon modified sequence that increases expression, optimizes an immunostimulatory signal, or removes a cryptic splice site.

10. The vector of claim 8, wherein the vector is a DNA plasmid.

11. The vector of claim 8, wherein the vector is a replication competent or replication defective vector.

12. The vector of claim 11, wherein the replication competent vector is selected from the group consisting of:

parainfluenza virus, Paramyxovirus, Newcastle disease virus, VSV, BCG, vaccinia, reovirus, rhinovirus, poliovirus, and adenovirus.

13. The vector of claim 11, wherein the replication defective vector is selected from the group consisting of:

poxviruses, alpha viruses, Venezuelan equine encephalitis viruses (EEV), Sinbis viruses, DNA viruses, adeno associated viruses (AAV), herpes simplex viruses (HSV), adenoviruses, and HPV virus-like particles.

14. A host cell comprising the vector of claim 8.