INFLUENZA VIRUS IMMUNOGENIC COMPOSITIONS AND USES THEREOF
Immunogenic compositions comprise a RNA component and a polypeptide component. The RNA component is a self-replicating RNA. The polypeptide component comprises an epitope from an influenza virus antigen (the first epitope), and the RNA component encodes a polypeptide which also comprises an epitope from an influenza virus antigen (the second epitope). Delivery of epitopes in these two different manners can enhance the immune response to influenza virus as compared to immunization with the RNA or the polypeptide alone.
1 . An immunogenic composition comprising: (i) a self-replicating RNA molecule that encodes a first polypeptide antigen comprising a first epitope from an influenza virus antigen; and (ii) a second polypeptide antigen comprising a second epitope from an influenza virus antigen; wherein:
(a) the first and second epitopes are both from influenza hemagglutinin;
(b) the first and second epitopes are both from influenza A virus; and/or
(c) the first epitope and the second epitope are both from influenza B virus.
2 . The immunogenic composition of claim 1 , wherein said first and second epitopes are both from an influenza A virus hemagglutinin.
3 . The immunogenic composition of claim 2 , wherein said first and second epitopes are both from the same subtype of an influenza A virus hemagglutinin.
4 . The immunogenic composition of claim 2 , wherein said first and second epitopes are both from influenza A virus H5 hemagglutinin.
5 . The immunogenic composition of claim 3 , wherein said first and second epitopes are both from the same influenza A virus hemagglutinin.
6 . The immunogenic composition of claim 1 , wherein said first and second epitopes are both from an influenza B virus hemagglutinin.
7 . The immunogenic composition of claim 6 , wherein said first and second epitopes are both from the same lineage of an influenza B virus hemagglutinin.
8 . The immunogenic composition of claim 7 , wherein said first and second epitopes are both from the same influenza B virus hemagglutinin.
9 . The immunogenic composition of claim 1 , wherein said first and second epitopes are the same.
10 . The immunogenic composition of claim 1 , wherein said first and second polypeptide antigens share at least two B-cell epitopes.
11 . The immunogenic composition of claim 1 , wherein (a) said first and second polypeptide antigens share a common amino acid sequence which includes multiple epitopes and is 80 amino acids or longer e.g. 120 amino acids or longer, and/or (b) said first and second polypeptide antigens have at least 80% amino acid sequence identity to each other.
12 . The immunogenic composition of claim 1 , wherein the self-replicating RNA is an alphavirus-derived RNA replicon.
13 . The immunogenic composition of claim 1 , wherein the self-replicating RNA molecule comprises one or more modified nucleotides.
14 . The immunogenic composition of claim 1 , including (i) liposomes (ii) non-toxic and biodegradable polymer microparticles or (iii) a cationic submicron oil-in-water emulsion.
15 . A method for treating or preventing influenza disease and/or infection, comprising administering to a subject in need thereof a therapeutically effective amount of a composition of claim 1 .
16 . A method for inducing an immune response in a subject comprising administering to a subject in need thereof a therapeutically effective amount of the composition of claim 1 .
17 . A kit comprising (a) a first kit component comprising a polypeptide that comprises an epitope from an influenza virus antigen, and (b) a second kit component comprising a self-replicating RNA which encodes a polypeptide that comprises an epitope from an influenza virus antigen.