EFFICIENT VACCINE
ABSTRACT OF DISCLOSURE Provided herein is a bivalent alphavirus replicon vaccine, which is a combination of a first polynucleotide which encodes alphavirus non-structural proteins nsp1, nsp2, nsp3 and nsp4 and an antigenic peptide and a second polynucleotide which encodes alphavirus non-structural proteins nsp1, nsp2, nsp3 and nsp4 and a CD8+ T cell epitope. The vaccine is useful against virus infection, especially, COVID-19 or SARS-COV-2 infection, the treatment of a cancer and/or an inflammatory disease.
1 . A bivalent alphavirus replicon vaccine, which is a combination of
a first polynucleotide which encodes alphavirus non-structural proteins nsp1, nsp2, nsp3 and nsp4 and an antigenic peptide and
a second polynucleotide which encodes alphavirus non-structural proteins nsp1, nsp2, nsp3 and nsp4 and a CD8+ T cell epitope.
2 . The bivalent alphavirus replicon vaccine of claim 1 , wherein the antigenic peptide is a protein derived from a virus, bacterium, a cancer or cytokine.
3 . The bivalent alphavirus replicon vaccine of claim 2 , wherein the antigenic peptide is a receptor binding domain (RBD) which is fused with transmembrane domain and a CD4+ T cell epitope.
4 . The bivalent alphavirus replicon vaccine of claim 2 , wherein the antigenic peptide is a protein derived from a virus or bacterium selected from the group consisting of Severe acute respiratory syndrome-related coronavirus (SARS), severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), Ebola virus, HIV, Hepatitis B virus (HBV), influenza virus, Hepatitis C virus (HCV), Human papillomavirus (HPV), Cytomegalovirus (CMV), Chikungunya virus, Respiratory syncytial virus (RSV), Dengue virus, a orthomyxoviridae family virus, and Mycobacterium tuberculosis.
5 . The bivalent alphavirus replicon vaccine of claim 4 , wherein the antigenic peptide is derived from a coronavirus.
6 . The bivalent alphavirus replicon vaccine of claim 3 , wherein the receptor binding domain (RBD) of the coronavirus S1 subunit.
7 . The bivalent alphavirus replicon vaccine of claim 6 , wherein the coronavirus is SARS-COV-2.
8 . The bivalent alphavirus replicon vaccine of claim 3 , wherein the transmembrane domain is derived from Influenza Hemagglutinin (HA), CD80, or a modified transmembrane domain derived from the antigenic peptide.
9 . The bivalent alphavirus replicon vaccine of claim 8 , wherein the transmembrane domain is derived from Influenza Hemagglutinin (HA).
10 . The bivalent alphavirus replicon vaccine of claim 3 , wherein the antigenic peptide comprises a RBD which is fused to transmembrane domain and a CD4+ T cell epitope.
11 . The bivalent alphavirus replicon vaccine of claim 10 , wherein the antigenic peptide is further fused to a signal sequence.
12 . The bivalent alphavirus replicon vaccine of claim 10 , wherein the CD4+ T cell epitope is a Pan-DR epitope (PADRE).
13 . The bivalent alphavirus replicon vaccine of claim 1 , wherein the CD8+ T cell epitopes is fused to a signal sequence.
14 . The bivalent alphavirus replicon vaccine of claim 1 , wherein the polynucleotide comprises a modified nucleotide.
15 . The bivalent alphavirus replicon vaccine of claim 1 , wherein at least one of the polynucleotides comprises 5-methyl-cytidine.
16 . A combination of vectors, comprising the first polynucleotide and the second polynucleotide recited in claim 1 respectively.
17 . The bivalent alphavirus replicon vaccine of claim 1 , which is a combination of a composition comprising the first polynucleotide or a vector comprising the first polynucleotide and a pharmaceutically acceptable delivery vehicle, and a composition comprising the second polynucleotide or a vector comprising the second polynucleotide and a pharmaceutically acceptable delivery vehicle.
18 . A bivalent alphavirus replicon vaccine composition, comprising the first and second polynucleotides recited claim 1 and a pharmaceutically acceptable delivery vehicle.
19 . A method of treating and/or preventing an infectious disease in a subject, comprising administering an effective amount of the bivalent vaccine of claim 1 to the subject in need thereof.
20 . The method according to claim 18 , wherein the infectious disease is caused by SARS-COV-2.