MODIFIED VACCINE DESIGN DEVELOPMENTS
Provided herein is an isolated polynucleotide, which encodes a polypeptide comprising an antigen protein fused to a signal sequence and a transmembrane domain, and optionally to ferritin. Also provided herein is an isolated polynucleotide, which encodes alphavirus non-structural proteins nsp1, nsp2, nsp3 and nsp4 and a polypeptide comprising an antigen protein fused to a signal sequence and a transmembrane domain, and optionally to ferritin. The antigen may be influenza. The polynucleotide such as RNA is useful as a vaccine against influenza infection.
1 . An isolated polynucleotide, which encodes a polypeptide comprising an antigen protein fused to a signal sequence and a transmembrane domain, and optionally to a ferritin.
2 . The polynucleotide of claim 1 , the antigen protein is an influenza protein.
3 . The polynucleotide of claim 1 , wherein the influenza protein is an influenza-virus hemagglutinin 1(HA1) and/or an influenza-virus hemagglutinin 2(HA2).
4 . The polynucleotide of claim 1 , wherein the influenza protein is a head region of HA1.
5 . The polynucleotide of claim 1 , wherein the ferritin is derived from Helicobacter pylori or a Helicobacter pylon-bullfrog hybrid ferritin.
6 . The polynucleotide of claim 1 , which is further encodes an alphavirus non-structural proteins nsp1, nsp2, nsp3 and nsp4.
7 . The polynucleotide of claim 1 , wherein the transmembrane domain and/or signal sequence is fused to the antigen protein by a linker.
8 . The polynucleotide of claim 1 , wherein the polynucleotide is RNA.
9 . The polynucleotide of claim 1 , wherein the polynucleotide is DNA.
10 . A vector comprising the polynucleotide of claim 1 .
11 . The vector of claim 10 , which comprises a promoter, 5′ UTR, polynucleotide encoding alphavirus non-structural proteins nsp1, nsp2, nsp3 and nsp4, SG promoter, a gene of interest encoding the polypeptide comprising an antigen protein fused to a signal sequence and a transmembrane domain, 3′UTR and poly A tail.
12 . A vaccine composition comprising the polynucleotide of claim 1 and a pharmaceutically acceptable carrier.
13 . The vaccine composition of claim 12 , wherein the pharmaceutically acceptable carrier is a delivery vehicle.
14 . The vaccine composition of claim 13 , wherein the delivery vehicle is a particle consisting of one or more alphavirus structural proteins or a lipid delivery system.
15 . A method of inducing immunomodulation in a subject, comprising administering an immunologically effective amount of the vaccine composition of claim 12 to the subject in need thereof.
16 . A method of treating, preventing and/or immunizing against an antigen in a subject, comprising administering an effective amount of the vaccine composition of claim 12 to the subject in need thereof.
17 . A polypeptide comprising an antigen protein fused to a signal sequence and a transmembrane domain, and optionally to ferritin.