Vaccine compositions against dengue virus diseases

1. A method of protecting a dengue immune human subject against dengue disease caused by a dengue virus of serotype 2, comprising

A) administering only 2 doses of an effective amount of a vaccine composition to the dengue immune human subject, wherein the doses are 6 months apart, and wherein said composition comprises:

a dengue antigen of each of serotypes 1 to 4, wherein said dengue antigens of serotypes 1 to 4 are each a live attenuated chimeric dengue virus comprising a yellow fever virus genome whose prM-E sequence has been substituted with the prM-E sequence of a dengue virus;

wherein the prM-E sequence of the dengue antigen of serotype 1 comprises SEQ ID NO: 1, the prM-E sequence of the dengue antigen of serotype 2 comprises SEQ ID NO: 2, the prM-E sequence of the dengue antigen of serotype 3 comprises SEQ ID NO: 3 and the prM-E sequence of the dengue antigen of serotype 4 comprises SEQ ID NO: 4:

wherein each dose of tetravalent vaccine comprises 5±1 log 10 CCID 50 of each live attenuated chimeric dengue virus;

wherein the route of administration is subcutaneous; and

wherein said dengue immune human subject is aged between 2 and 60 years old; and

B) protecting the dengue immune human subject against dengue disease caused by a dengue virus of serotype 2.

2. The method of claim 1 , wherein said dengue disease is severe dengue disease.

3. The method of claim 1 , wherein said method results in a reduction in the incidence or likelihood of hospitalization due to said dengue disease.

4. The method of claim 1 , wherein said method also protects said human subject against dengue disease caused by a dengue virus of serotype 1, dengue disease caused by a dengue virus of serotype 3 and dengue disease caused by a dengue virus of serotype 4.

5. The method of claim 4 , wherein said dengue disease caused by a dengue virus of serotype 1 is severe dengue disease, said dengue disease caused by a dengue virus of serotype 2 is severe dengue disease, said dengue disease caused by a dengue virus of serotype 3 is severe dengue disease and said dengue disease caused by a dengue virus of serotype 4 is severe dengue disease.

6. The method of claim 1 , wherein said subject is aged between 6 and 60 years old, between 9 and 60 years old, or between 12 and 60 years old.

7. The method of claim 1 , wherein said subject is at least 9 years of age.

8. The method of claim 6 , wherein said subject is aged between 2 and 16 years old, between 6 and 16 years old, or between 9 and 16 years old.

9. The method of claim 1 , wherein said subject is yellow fever immune.

10. The method of claim 1 , wherein said subject resides in a dengue endemic area.

11. The method of claim 1 , wherein said dengue disease caused by a dengue virus of serotype 2 is dengue disease caused by a dengue virus of serotype 2 having an American, Asian/American, or a Cosmopolitan genotype.

12. The method of claim 1 , wherein said composition further comprises a pharmaceutically acceptable carrier or excipient.

13. The method of claim 1 , wherein said method of protecting results in a statistically significant reduction in the incidence or likelihood of repeated symptomatic virologically-confirmed dengue cases.

14. The method of claim 1 , wherein the human subject is protected against dengue disease caused by a dengue virus of serotype 2 after a first dose of the vaccine composition.

15. The method of claim 1 , wherein the human subject is monotypic dengue immune.

16. The method of claim 1 , wherein the human subject is multitypic dengue immune.

17. The method of claim 12 , wherein the pharmaceutically acceptable carrier is 0.4% NaCl buffer containing excipients consisting of essential amino acids, non-essential amino acids, L-arginine chlorhydrate, saccharose, D-trehalose, dehydrate, sorbitol, tris (hydroxymethyl) aminoethane and urea.

18. The method of claim 1 , wherein the vaccine composition is administered in a volume between 0.1 and 1.0 ml.

19. The method of claim 1 , wherein the vaccine composition is administered in a volume of 0.5 ml.

20. The method of claim 1 , wherein the dengue immune human subject is in good health based on medical history and physical examination.

21. A method of protecting a dengue immune human subject against dengue disease caused by a dengue virus of serotype 2, comprising

A) administering only 2 doses of an effective amount of a vaccine composition to the dengue immune human subject, wherein the doses are 6 months apart, and wherein said composition comprises:

a dengue antigen of each of serotypes 1 to 4, wherein said dengue antigens of serotypes 1 to 4 are each a live attenuated chimeric dengue virus comprising a yellow fever virus genome whose prM-E sequence has been substituted with the prM-E sequence of a dengue virus;

wherein the prM-E sequence of the dengue antigen of serotype 1 comprises SEQ ID NO: 1, the prM-E sequence of the dengue antigen of serotype 2 comprises SEQ ID NO: 2, the prM-E sequence of the dengue antigen of serotype 3 comprises SEQ ID NO: 3 and the prM-E sequence of the dengue antigen of serotype 4 comprises SEQ ID NO: 4;

wherein each dose of tetravalent vaccine comprises 5±1 log 10 CCID 50 of each live attenuated chimeric dengue virus;

wherein the route of administration is subcutaneous;

wherein the vaccine composition further comprises a pharmaceutically acceptable carrier which is 0.4% NaCl buffer containing excipients consisting of essential amino acids, non-essential amino acids, L-arginine chlorhydrate, saccharose, D-trehalose, dehydrate, sorbitol, tris (hydroxymethyl) aminoethane and urea;

wherein the vaccine composition is administered in a volume between 0.1 and 1.0 ml;

wherein said subject is aged between 2 and 60 years old;

wherein the dengue immune human subject is in good health based on medical history and physical examination; and

wherein said subject resides in a dengue endemic area; and

B) protecting the dengue immune human subject against dengue disease caused by a dengue virus of serotype 2.

22. The method of claim 21 , wherein the human subject is monotypic dengue immune.

23. The method of claim 21 , wherein the human subject is multitypic dengue immune.

24. The method of claim 21 , wherein the human subject is aged between 6 and 60 years old.

25. The method of claim 21 , wherein the human subject is aged between 9 and 16 years old.

26. The method of claim 21 , wherein the prM-E sequence of the dengue antigen of serotype 2 comprises SEQ ID NO: 2.

27. The method of claim 21 , wherein the prM-E sequence of the dengue antigen of serotype 2 comprises SEQ ID NO: 2.