Adenoviral vector-based malaria vaccines

Patent metadata

Field	Value
Publication number	US-9254316-B2
Application number	US-201313890422-A
Country	US
Kind code	B2
Filing date	May 9, 2013
Priority date	Jan 9, 2007
Publication date	Feb 9, 2016
Grant date	Feb 9, 2016

Abstract

The invention provides a method of inducing an immune response against malaria in a mammal. The method comprises intramuscularly administering to a mammal a composition comprising a pharmaceutically acceptable carrier and either or both of (a) a first adenoviral vector comprising a nucleic acid sequence encoding a P. falciparum circumsporozoite protein (CSP) operably linked to a human CMV promoter, and/or (b) a second adenoviral vector comprising a nucleic acid sequence encoding a P. falciparum apical membrane antigen 1 (AMA-1) antigen operably linked to a human CMV promoter.

First claim

The invention claimed is:

1. A method of inducing an immune response against malaria in a mammal, which method comprises:
(a) administering a priming composition to the mammal, wherein the priming composition comprises a plasmid encoding a P. falciparum circumsporozoite protein (CSP), or an immunogenic portion thereof, and/or a P. falciparum apical membrane antigen 1 (AMA-1) antigen, or an immunogenic portion thereof; and
(b) intramuscularly administering to a mammal a composition comprising a pharmaceutically acceptable carrier and either or both of:
(1) about 1×10 6 particle units (pu) to about 1×10 12 pu of a first adenoviral vector comprising an adenoviral genome comprising a left inverted terminal repeat (ITR), the E2A region, the E2B region, late regions LI-LS, and a right ITR, and a nucleic acid sequence encoding a P. falciparum circumsporozoite protein (CSP) operably linked to a human CMV promoter, and
(2) about 1×10 6 particle units pu to about 1×10 12 pu of a second adenoviral vector comprising an adenoviral genome comprising a left inverted terminal repeat (ITR), the E2A region, the E2B region, late regions LI-LS, and a right ITR, and a nucleic acid sequence encoding a P. falciparum apical membrane antigen 1 (AMA-1) antigen operably linked to a human CMV promoter, wherein the composition is administered to the mammal one or more times, and wherein the nucleic acid sequence encoding a P. falciparum CSP and/or the nucleic acid sequence encoding a P. falciparum AMA-1 are expressed to produce the CSP and/or the AMA-1 in the mammal to induce an immune response against malaria.

2. The method of claim 1 , wherein the composition comprises the first adenoviral vector and the second adenoviral vector.

3. The method of claim 2 , wherein the composition comprises About 5×10 9 pu to about 5×10 10 pu of the first adenoviral vector and about 5×10 9 pu to about 5×10 10 pu of the second adenoviral vector.

4. The method of claim 3 , wherein the composition comprises about 1×10 10 pu of the first adenoviral vector and about 1×10 10 pu of the second adenoviral vector.

5. The method of claim 2 , wherein the composition comprises about 1×10 10 pu to about 1×10 11 pu of the first adenoviral vector and about 1×10 10 pu to about 1×10 11 pu of the second adenoviral vector.

6. The method of claim 5 , wherein the composition comprises about 5×10 10 pu of the first adenoviral and about 5×10 10 pu of the second adenoviral vector.

7. The method of claim 1 , wherein the composition comprises the first adenoviral vector and does not comprise the second adenoviral vector.

8. The method of claim 7 , wherein the composition comprises about 1×10 10 pu to about 1×10 11 pu of the first adenoviral vector.

9. The method of claim 8 , wherein the composition comprises about 5×10 10 pu of the first adenoviral vector.

10. The method of claim 1 , wherein the composition comprises the second adenoviral vector and does not comprise the first adenoviral vector.

11. The method of claim 10 , wherein the composition comprises about 1×10 10 pu to about 1×10 11 pu of the second adenoviral vector.

12. The method of claim 11 , wherein the composition comprises about 5×10 10 pu of the second adenoviral vector.

13. The method of claim 1 , wherein each of the first and second adenoviral vectors is replication-deficient and requires complementation of both the E1 region and the E4 region of the adenoviral genome for propagation.

14. The method of claim 13 , wherein the adenoviral genome of each of the first and second adenoviral vectors lacks the entire E1 region and at least a portion of the E4 region of the adenoviral genome.

15. The method of claim 14 , wherein the nucleic acid sequence encoding P. falciparum CSP is inserted into the deleted E1 region of the adenoviral genome of the first adenoviral vector.

16. The method of claim 15 , wherein the nucleic acid sequence encoding the P. falciparum AMA-1 antigen is inserted into the deleted E1 region of the adenoviral genome of the second adenoviral vector.

17. The method of claim 1 , wherein the nucleic acid sequence encoding P. falciparum CSP comprises codons expressed more frequently in mammals than in Plasmodium.

18. The method of claim 17 , wherein the nucleic acid sequence encoding P. falciparum CSP comprises SEQ ID NO: 10.

19. The method of claim 1 , wherein the nucleic acid sequence encoding P. falciparum AMA-1 antigen comprises codons expressed more frequently in mammals than in Plasmodium.

20. The method of claim 19 , wherein the nucleic acid sequence encoding P. falciparum AMA-1 antigen comprises SEQ ID NO: 16.

21. The method of claim 1 , wherein the mammal is a human.

22. The method of claim 1 , wherein the composition is administered to the mammal once.

23. The method of claim 1 , wherein the composition is administered to the mammal twice.

24. The method of claim 1 , wherein the priming composition is administered to the mammal at least 10 days before administration of the composition comprising the first and/or second adenoviral vectors.

Assignees

• Bruder Joseph T
• King C Richter
• Richie Thomas
• Limbach Keith
• Doolan Denise Louise
• Us Navy

Inventors

• Bruder Joseph T
• King C Richter
• Richie Thomas
• Limbach Keith
• Doolan Denise Louise

Classifications

• C12N2710/10043

  viral genome or elements thereof as genetic vector · CPC title

• A61K2039/53

  DNA (RNA) vaccination · CPC title

• C12N7/00

  Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) · CPC title

• A61K39/015 Primary

  Hemosporidia antigens, e.g. Plasmodium antigens · CPC title

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title