Compositions and methods for inducing protective immunity against human immunodeficiency virus infection

1. A vaccine combination for inducing an immune response against a human immunodeficiency virus (HIV) in a subject, comprising:

(i) a primer composition comprising an immunogenically effective amount of one or more adenovirus 26 (rAd26) vectors encoding one or more HIV antigenic polypeptides comprising amino acid sequences selected from the group consisting of SEQ ID NOs: 1-4, and a pharmaceutically acceptable carrier;

(ii) a first booster composition comprising an immunogenically effective amount of an isolated HIV envelope polypeptide comprising at least one of a stabilized trimer of HIV gp140 comprising the amino acid sequence of SEQ ID NO: 5 and a stabilized trimer of HIV gp140 comprising the amino acid sequence of SEQ ID NO: 6, and a pharmaceutically acceptable carrier; and

(iii) a second booster composition comprising an immunogenically effective amount of one or more MVA vectors encoding one or more HIV antigenic polypeptides comprising amino acid sequences selected from the group consisting of SEQ ID NOs: 1-4, respectively,

wherein the first booster composition is for administration together with the second booster composition to the subject after administration of the primer composition.

2. The vaccine combination of claim 1 , wherein the first and second booster compositions are present in separate compositions.

3. The vaccine combination of claim 1 , wherein the primer composition comprises an immunogenically effective amount of one or more rAd26 vectors encoding HIV antigenic polypeptides having the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 3, and SEQ ID NO: 4, and a pharmaceutically acceptable carrier; and the second booster composition comprises an immunogenically effective amount of one or more MVA vectors encoding HIV antigenic polypeptides having the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 3, and SEQ ID NO: 4.

4. The vaccine combination of claim 3 , wherein the one or more MVA vectors further encode an HIV antigenic polypeptide having the amino acid sequence of SEQ ID NO: 2.

5. The vaccine combination of claim 1 , wherein the isolated HIV envelope polypeptide comprises a stabilized trimer of HIV gp140 comprising the amino acid sequence of SEQ ID NO: 5.

6. The vaccine combination of claim 1 , wherein the isolated HIV envelope polypeptide comprises a stabilized trimer of HIV gp140 comprising the amino acid sequence of SEQ ID NO: 6.

7. The vaccine combination of claim 3 , wherein the isolated HIV envelope polypeptide comprises a stabilized trimer of HIV gp140 comprising the amino acid sequence of SEQ ID NO: 5.

8. The vaccine combination of claim 1 , wherein the first booster composition further comprises an adjuvant.

9. The vaccine combination of claim 8 , wherein the adjuvant is aluminum phosphate or a saponin-based adjuvant.

10. A method of inducing an immune response against a human immunodeficiency virus (HIV) in a subject, the method comprising:

(i) administering to the subject a primer composition comprising an immunogenically effective amount of one or more adenovirus 26 (rAd26) vectors encoding one or more HIV antigenic polypeptides comprising amino acid sequences selected from the group consisting of SEQ ID NOs: 1-4, respectively, and a pharmaceutically acceptable carrier; and

(ii) administering to the subject a first booster composition comprising an immunogenically effective amount of an isolated HIV envelope polypeptide comprising at least one of a stabilized trimer of HIV gp140 comprising the amino acid sequence of SEQ ID NO: 5 and a stabilized trimer of HIV gp140 comprising the amino acid sequence of SEQ ID NO: 6, and a pharmaceutically acceptable carrier; and

(iii) administering to the subject a second booster composition together with the first booster composition, the second booster composition comprising an immunogenically effective amount of one or more MVA vectors encoding one or more HIV antigenic polypeptides comprising amino acid sequences selected from the group consisting of SEQ ID NOs: 1-4, respectively, and a pharmaceutically acceptable carrier;

wherein the first and second booster compositions are administered after the primer composition is administered.

11. The method of claim 10 , wherein the first and second booster compositions are present in separate compositions.

12. The method of claim 10 , wherein the first primer composition comprises an immunogenically effective amount of one or more rAd26 vectors encoding HIV antigenic polypeptides having the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 3, and SEQ ID NO: 4, and a pharmaceutically acceptable carrier; and the second booster composition comprises an immunogenically effective amount of one or more MVA vectors encoding HIV antigenic polypeptides having the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 3, and SEQ ID NO: 4.

13. The method of claim 12 , wherein the one or more MVA vectors further encode an HIV antigenic polypeptide having the amino acid sequence of SEQ ID NO: 2.

14. The method of claim 10 , wherein the isolated HIV envelope polypeptide comprises a stabilized trimer of HIV gp140 having the amino acid sequence of SEQ ID NO: 5.

15. The method of claim 10 , wherein the isolated HIV envelope polypeptide comprises a stabilized trimer of HIV gp140 having the amino acid sequence of SEQ ID NO: 6.

16. The method of claim 12 , wherein the isolated HIV envelope polypeptide comprises a stabilized trimer of HIV gp140 having the amino acid sequence of SEQ ID NO: 5.

17. The method of claim 10 , wherein the second composition further comprises an adjuvant.

18. The method of claim 17 , wherein the adjuvant is aluminum phosphate or a saponin-based adjuvant.

19. The method of claim 10 , wherein the immune response generated is a protective immune response.

20. The method of claim 10 , wherein the subject is a human.