Tuberculosis Compositions And Methods Of Using The Same

• US 20190322709A1
• Filed: 03/01/2019
• Published: 10/24/2019
• Est. Priority Date: 06/25/2013
• Status: Active Grant

• Current Assignee: International AIDS Vaccine Initiative, Inc.
• Original Assignee: International AIDS Vaccine Initiative, Inc.
• Inventors: Anantha, Ravi, Cadieux, Nathalie, Evans, Thomas G., Stone, Michele, Walker, Barry
• Granted Patent: US 11,014,969 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/523 expressing foreign proteins
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2039/55561 CpG containing adjuvants; Oligonucleotide containing adjuvants
• CPC Class Codes: A61K 2039/55572 Lipopolysaccharides; Lipid A; Monophosphoryl lipid A
• CPC Class Codes: A61K 2039/70 Multivalent vaccine
• CPC Class Codes: A61K 39/04 Mycobacterium, e.g. Mycobacterium tuberculosis
• CPC Class Codes: A61P 31/06 for tuberculosis
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 14/35 from Mycobacteriaceae (F)
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

Abstract

The present disclosure provides fusion proteins comprising Mycobacterium tuberculosis (Mtb) antigens, nucleic acid molecules encoding the same, vectors comprising nucleic acid molecules, compositions comprising the same, and methods of eliciting an immune response against tuberculosis.

Claims

1. A fusion protein comprising at least six Mycobacterium tuberculosis (Mtb) antigens, wherein the Mtb antigens comprise:

at least one acute Mtb antigen, at least one latent Mtb antigen, and at least one resuscitation Mtb antigen, wherein the acute Mtb antigen is ESAT6, the latent Mtb antigen is Rv3407 or Rv2626c, and the resuscitation Mtb antigen is RpfD;

or

at least two latent Mtb antigens, and at least one resuscitation Mtb antigen, wherein the latent Mtb antigens are Rv3407 and Rv2626c, and the resuscitation Mtb antigen is RpfD.

2. The fusion protein according to claim 1 wherein ESAT6 comprises the amino acid sequence of SEQ ID NO:

8 Rv2626c comprises the amino acid sequence of SEQ ID NO;

32 Rv3407 comprises the amino acid sequence of SEQ ID NO;

36; and

RpfD comprises the amino acid sequence of SEQ ID NO;

47 or SEQ ID NO;

48.

6. A pharmaceutical composition comprising the fusion protein according to claim 1 and a pharmaceutically acceptable carrier.

7. A vector encoding the fusion protein according to claim 1.

8. The vector according to claim 7 which is adenovirus 4, adenovirus 5, chimpanzee adenovirus 3, chimpanzee adenovirus 63, or chimpanzee adenovirus 68.

9. A cell comprising the vector according to claim 7.

10. The cell according to claim 9 which is a recombinant BCG.

19. A method of eliciting an immune response against Mycobacterium tuberculosis in a mammal comprising administering to the mammal an immunologically sufficient amount of the fusion protein according to claim 1.

21. The method according to claim 19, wherein the mammal is a human.

22. The method according to claim 19, wherein ESAT6 comprises the amino acid sequence of SEQ ID NO:

8, Rv2626c comprises the amino acid sequence of SEQ ID NO;

32, Rv3407 comprises the amino acid sequence of SEQ ID NO;

36, and RpfD comprises the amino acid sequence of SEQ ID NO;

47 or SEQ ID NO;

48.

23. The vector according to claim 7, wherein ESAT6 is encoded by the nucleic acid sequence of SEQ ID NO:

6 or SEQ ID NO;

7;

Rv2626c is encoded by the nucleic acid sequence of SEQ ID NO;

29, SEQ ID NO;

30, or SEQ ID NO;

31;

Rv3407 is encoded by the nucleic acid sequence of SEQ ID NO;

33, SEQ ID NO;

34, or SEQ ID NO;

35; and

RpfD is encoded by the nucleic acid sequence of SEQ ID NO;

44, SEQ ID NO;

45, or SEQ ID NO;

46.

3-5. -5. (canceled)

11-18. -18. (canceled)

20. (canceled)