Methods of potentiating HIV-1-specific CD8+ immune responses involving the concomitant administration of DNA and ALVAC expression vectors

• US 7,771,729 B2
• Filed: 07/05/2006
• Issued: 08/10/2010
• Est. Priority Date: 04/28/2000
• Status: Expired due to Fees

• Current Assignee: United States Department Of Health And Human Services (Government of the United States of America)
• Original Assignee: United States Department Of Health And Human Services (Government of the United States of America)
• Inventors: Franchini, Genoveffa, Tartaglia, James, Pavlakis, George, Hel, Zdenek
• Primary Examiner(s): Parkin; Jeffrey S.
• Application Number:
  US11/428,815
• Publication Number:
  US 20060240042A1
• Time in Patent Office: 1,497 Days
• Field of Search: None
• US Class Current: 424/199.1
• CPC Class Codes: A61K 2039/5256 expressing foreign proteins
• CPC Class Codes: A61K 2039/53 DNA (RNA) vaccination
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• 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 39/21 Retroviridae, e.g. equine infectious anemia virus
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2710/24043 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 2740/15022 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2740/15034 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2740/16034 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2740/16122 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2740/16222 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: C12N 2740/16322 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
• CPC Class Codes: Y10S 530/826 Viruses

Abstract

This invention relates to improved methods of inducing an immune response for the prevention or treatment of HIV-1 infection by using a nucleic acid vaccine in conjunction with a recombinant viral vaccine, e.g., a poxvirus vaccine, to potentiate and broaden the immune response. The present invention further provides a particularly effective vaccine regimen comprising a DNA vaccine used in combination with a poxvirus virus, especially NYVAC or ALVAC.

Claims

1. A method of potentiating a CD8+ response to human immunodeficiency virus-1 (HIV-1) epitopes in a human comprising:

administering an expression vector encoding HIV-1 Gag, Pol, Pro, Tat, Nef, Rev, Vif, Vpr or Env antigens; and

administering a recombinant ALVAC pox virus encoding the same antigens encoded by the expression vector;

wherein the expression vector and the recombinant pox virus enter the cells of the human

and intracellularly produce HIV peptides that are presented on the cell'"'"'s MHC class I molecules in an amount sufficient to stimulate a CD8+ response, and further, wherein administration of the combination of the expression vector and the recombinant pox virus potentiates the immune response compared to administration of either the expression vector or the recombinant pox virus by itself.

2. The method of claim 1, wherein the recombinant pox virus is an attenuated recombinant pox virus vaccine.

3. The method of claim 1, wherein the expression vector is a DNA expression vector.

4. The method of claim 1, wherein the HIV peptides are structural viral peptides.

5. The method of claim 1, wherein the HIV peptides are non-structural viral peptides.

6. The method of claim 1, wherein the expression vector or the recombinant ALVAC pox virus is administered with an adjuvant.

7. The method of claim 1, further comprising two administrations of the expression vector.

8. The method of claim 1, further comprising three administrations of the expression vector.

9. The method of claim 1, wherein the expression vector is administered before the recombinant pox virus.

10. The method of claim 1, wherein the human is infected with HIV-1.

11. The method of claim 10, wherein the human has a viral load of less than 10,000 copies per milliliter.

12. The method of claim 1, wherein the human is not infected with the HIV-1.

13. The method of claim 1, wherein the HIV peptides are HIV-1 envelope, gag or

protease peptides.

14. A method of reducing viral load in a mammal that is infected with an immunodeficiency virus, comprising:

administering to the mammal an expression vector that expresses encoded immunodeficiency virus Gag, Pol and Env antigens; and

later administering to the mammal a recombinant ALVAC pox virus encoding said antigens;

wherein the expression vector and the recombinant pox virus enter the cells of the mammal and intracellularly produce said antigens, and

wherein administration of the combination of the expression vector and the recombinant pox virus reduces the viral load more than administration of either the expression vector or the recombinant pox virus by itself.