Tuberculosis compositions and methods of using the same

• US 10,266,574 B2
• Filed: 06/24/2014
• Issued: 04/23/2019
• 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
• Primary Examiner(s): Gangle, Brian
• Application Number:
  US14/313,694
• Publication Number:
  US 20140377300A1
• Time in Patent Office: 1,764 Days
• Field of Search: None
• 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 consisting of four or five antigens, wherein the four or five antigens are Mycobacterium tuberculosis antigens, and wherein the fusion protein comprises an amino acid sequence that is at least 98% identical to an amino acid sequence of:

ESAT6-Rv1733c-Rv2626c-RpfD (SEQ ID NO;

53 or SEQ ID NO;

54);

ESAT6-Rv1733c-Rv2626c-RpfB (SEQ ID NO;

56);

RpfB-ESAT6-Rv1733c-Rv2626c (SEQ ID NO;

58);

Ag85B-ESAT6-Rv1733c-Rv2626c-RpfD (SEQ ID NO;

61 or SEQ ID NO;

62);

Ag85B-ESAT6-Rv1733c-Rv2626c-RpfB (SEQ ID NO;

99 or SEQ ID NO;

100);

PPE51-Rv1733c-Rv2628c-RpfD (SEQ ID NO;

64);

PPE51-Rv1733c-Rv2628c-RpfB (SEQ ID NO;

66);

Rv3407-Rv1733c-Rv2626c-RpfB (SEQ ID NO;

68);

or

Rv3407-Rv1733c-Rv2626c-RpfD (SEQ ID NO;

70).

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

3. The fusion protein according to claim 1, wherein the fusion protein comprises an amino acid sequence at least 98% identical to an amino acid sequence of Ag85B-ESAT6-Rv1733c-Rv2626c-RpfD (SEQ ID NO:

61 or SEQ ID NO;

62).

6. 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.

4. A fusion protein selected from the group consisting of

ESAT6-Rv1733c-Rv2626c-RpfD (SEQ ID NO:

53 or SEQ ID NO;

54);

ESAT6-Rv1733c-Rv2626c-RpfB (SEQ ID NO;

56);

RpfB-ESAT6-Rv1733c-Rv2626c (SEQ ID NO;

58);

Ag85B-ESAT6-Rv1733c-Rv2626c-RpfD (SEQ ID NO;

61 or SEQ ID NO;

62);

Ag85B-ESAT6-Rv1733c-Rv2626c-RpfB (SEQ ID NO;

99 or SEQ ID NO;

100);

PPE51-Rv1733c-Rv2628c-RpfD (SEQ ID NO;

64);

PPE51-Rv1733c-Rv2628c-RpfB (SEQ ID NO;

66);

Rv3407-Rv1733c-Rv2626c-RpfB (SEQ ID NO;

68);

or

Rv3407-Rv1733c-Rv2626c-RpfD (SEQ ID NO;

70).

5. The fusion protein according to claim 4, where in the fusion protein is Ag85B-ESAT6-Rv1733c-Rv2626c-RpfD (SEQ ID NO:

61 or SEQ ID NO;

62).