DNA vaccines against rotavirus infections

• US 6,165,993 A
• Filed: 03/02/1998
• Issued: 12/26/2000
• Est. Priority Date: 03/23/1992
• Status: Expired due to Fees

• Current Assignee: University Of Massachusetts
• Original Assignee: University Of Massachusetts
• Inventors: Robinson, Harriet L., Fynan, Ellen F., Herrmann, John E.
• Primary Examiner(s): Clark, Deborah J. R.
• Application Number:
  US09/233,813
• Time in Patent Office: 1,030 Days
• Field of Search: 435/320.1, 435/235.1, 514/44, 424/93.2, 536/23.1, 536/23.5, 536/23.4
• US Class Current: 514/44.00R
• 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 2039/57 characterised by the type of response, e.g. Th1, Th2
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/15 Reoviridae, e.g. calf diarrhea virus
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C12N 2720/12322 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2720/12334 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Abstract

This invention relates to methods of eliciting an immune response and/or protective immunity in a vertebrate by introducing into the vertebrate a DNA vaccine which consists essentially of DNA encoding an antigen or antigens, e.g., capsid proteins or polypeptides, of rotavirus. The uptake of the DNA vaccine by a host vertebrate results in the expression of the capsid protein, thereby eliciting humoral or cell-mediated immune responses, or both, which can provide protection against infection and/or prevent clinically significant rotavirus-caused disease. In addition, the invention demonstrates that an internal viral antigen provides protective immunity in a host. The host can be any vertebrate, including birds, piglets, and humans.

Claims

1. A method of eliciting an immune response against a rotavirus in a vertebrate, said method comprising administrating to the vertebrate a plasmid vector comprising one or more isolated nucleotide sequences each encoding a rotavirus polypeptide selected from the group consisting of VP4, VP6, and VP7, and transcriptional and translational regulatory sequences operably linked to the isolated nucleotide sequences, whereby expression of said nucleotide sequences in one or more cells in the vertebrate elicits a humoral immune response, a cell-mediated immune response, or both, against the rotavirus.

2. A method of eliciting a protective immunity against a rotavirus infection in a vertebrate, said method comprising administering to the vertebrate a plasmid vector comprising one or more isolated nucleotide sequence each encoding a rotavirus polypeptide selected from the group consisting of VP4, VP6, and VP7, and transcriptional and translational regulatory sequences operably linked to the isolated nucleotide sequences, whereby expression of said nucleotide sequences in one or more cells in the vertebrate elicits a humoral immune response, a cell-mediated immune response, or both against the rotavirus in the vertebrate, and whereby the vertebrate is protected from the disease caused by subsequent exposure to the rotavirus.

3. A method of claim 2, wherein the regulatory sequences are of nonretroviral origin.

4. A method of claim 2, wherein at least one of said regulatory sequences is the cytomegalovirus immediate-early enhancer promoter.

5. A method of claim 2, wherein at least one of said regulatory sequences is intron A.

6. A method of claim 2, wherein said rotavirus polypeptide is VP4.

7. A method of claim 2, wherein said rotavirus polypeptide is VP6.

8. A method of claim 2, wherein said rotavirus polypeptide is VP7.

9. A method of claim 2, wherein said vertebrate is a pig.

10. A method of claim 2, wherein said vertebrate is a human.

11. A method of claim 2, wherein the plasmid vector is administered to the vertebrate through a route of administration selected from the group consisting of inhalation, intravenous, intramuscular, intraperitoneal, intradermal, and subcutaneous.

12. A method of claim 2, wherein the plasmid vector is administered to the vertebrate by contacting the plasmid vector with a mucosal surface of the vertebrate.

13. A method of claim 2, wherein the plasmid vector is micorosphere encapsulated, and is administered to the vertebrate by contacting the microsphere-encapsulated plasmid vector with a mucosal surface of the vertebrate.

14. A method of claim 2, wherein the plasmid vector is coated onto gold beads for administration to the vertebrate by particle bombardment delivery.

15. A method of claim 14, wherein the gold beads are approximately 1 μ

m to 2 μ

m in diameter.

16. A method of claim 2, wherein the protective immunity is homologous, homotypic, heterotypic, or heterologous.

17. A method of claim 2, wherein the vertebrate is a mammal.