Immunogenic compositions and uses thereof

Patent metadata

Field	Value
Publication number	US-11058762-B2
Application number	US-201214130869-A
Country	US
Kind code	B2
Filing date	Jul 6, 2012
Priority date	Jul 6, 2011
Publication date	Jul 13, 2021
Grant date	Jul 13, 2021

Abstract

This invention generally relates to immunogenic compositions that comprise an RNA component and a polypeptide component. Immunogenic compositions that deliver antigenic epitopes in two different forms—a first epitope from a pathogen, in RNA-coded form; and a second epitope from the same pathogen, in polypeptide form—are effective in inducing immune response to the pathogen. The invention also relates to a kit comprising an RNA-based priming composition and a polypeptide-based boosting composition. The kit may be used for sequential administration of the priming and the boosting compositions.

First claim

What is claimed:

1. An immunogenic composition comprising an effective amount of: (i) a plurality of self-replicating RNA molecules that encode a first polypeptide antigen comprising a first epitope and (ii) a second polypeptide antigen comprising a second epitope, wherein said first epitope and second epitope are epitopes from the same pathogen, and
wherein the self-replicating RNA molecules:
a) are not encapsulated in virus-like particles, and
b) cannot perpetuate themselves in infectious form, and
wherein at least haft of the self-replicating RNA molecules are encapsulated within individual liposomes that encapsulate said self-replicating RNA molecules; said composition is formulated for administration to a subject; said composition induces an immunogenic response against said pathogen when administered to a subject in vivo.

2. The immunogenic composition of claim 1 , wherein said first epitope and second epitope are the same epitope.

3. The immunogenic composition of claim 1 , wherein said first epitope and second epitope are different epitopes.

4. The immunogenic composition of claim 1 , wherein said first polypeptide antigen and second polypeptide antigen are substantially the same.

5. The immunogenic composition of claim 1 , wherein said first polypeptide antigen is a soluble or membrane anchored polypeptide, and said second polypeptide antigen is a soluble polypeptide.

6. The immunogenic composition of claim 1 , wherein said first polypeptide antigen is a fusion polypeptide further comprising a third epitope from a different pathogen.

7. The immunogenic composition of claim 1 , wherein said second polypeptide antigen is a fusion polypeptide further comprising a third epitope from a different pathogen.

8. The immunogenic composition of claim 1 , wherein said first epitope and second epitope are epitopes from the same subspecies of the pathogen.

9. The immunogenic composition of claim 1 , wherein the self-replicating RNA is an alphavirus-derived RNA replicon.

10. The immunogenic composition of claim 1 , wherein the self-replicating RNA molecule comprises one or more modified nucleotides.

11. The immunogenic composition of claim 1 , wherein the pathogen is a virus, and the first polypeptide antigen and second polypeptide antigen are viral antigens.

12. The immunogenic composition of claim 11 , wherein the viral antigens are from respiratory syncytial virus (RSV) or Cytomegalovirus (CMV).

13. The immunogenic composition of claim 12 , wherein the viral antigens are RSV-F antigens.

14. The immunogenic composition of claim 13 , wherein the RSV-F antigens comprise an amino acid sequence selected from SEQ ID NOs: 25-40.

15. The immunogenic composition of claim 12 , wherein the viral antigens are CMV antigens, and wherein the CMV antigens are independently selected from the group consisting of a gB antigen, a gH antigen, a gL antigen, a gM antigen, a gN antigen, a gO antigen, a UL128 antigen, a UL129 antigen, and a UL130 antigen.

16. The immunogenic composition of claim 1 , further comprising an adjuvant.

17. The composition of claim 1 , wherein the liposomes are formed from a mixture comprising one or more of a cationic lipid and a pegylated lipid.

18. The composition of claim 17 , wherein the liposomes are formed from a mixture comprising both of (1) said one or more of a cationic lipid and (2) said pegylated lipid.

19. The composition of claim 18 , wherein the liposomes are formed from a mixture further comprising cholesterol.

20. A method for inducing an immune response in a subject comprising administering to a subject in need thereof a therapeutically effective amount of a composition according to claim 1 .

21. An immunogenic composition comprising an effective amount of: (i) a plurality of self-replicating RNA molecules that encode a first polypeptide antigen comprising a first epitope and (ii) a second polypeptide antigen comprising a second epitope, wherein said first epitope and second epitope are epitopes from the same pathogen, and
wherein the self-replicating RNA molecules:
a) are not encapsulated in virus-like particles, and
b) cannot perpetuate themselves in infectious form, and
wherein at least half of said self-replicating RNA molecules are encapsulated within individual liposomes, which form an outer layer around an aqueous core containing said self-replicating RNA molecules; said composition is formulated for administration to a subject; and said composition induces an immunogenic response against said pathogen and encoded products of RNA replication and amplification of the self-replicating RNA when administered to a subject in vivo.

Assignees

• Geall Andrew
• Otten Gillis
• Barnett Susan
• Glaxosmithkline Biologicals Sa

Inventors

• Geall Andrew
• Otten Gillis
• Barnett Susan

Classifications

• 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

• A61K39/12

  Viral antigens · CPC title

• A61K2039/55588

  Adjuvants of undefined constitution · CPC title

• A61K39/245

  Herpetoviridae, e.g. herpes simplex virus · CPC title

• A61P31/14

  for RNA viruses · CPC title