Broad-spectrum multi-antigen pan-coronavirus vaccine
View Patent ↗Waning immunity induced by first-generation Spike-alone-based COVID-19 has failed to prevent immune escape by many variants of concern (VOCs) that emerged from 2020 to 2024, resulting in a prolonged COVID-19 pandemic. Thus, a next-generation Coronavirus (CoV) vaccine incorporating highly conserved non-Spike SARS-CoV-2 antigens is described herein. Conserved non-Spike T cell antigens in combination with a Spike antigen encapsulated in lipid nanoparticles: (i) Induced high frequencies of lung-resident antigen-specific CXCR5+CD4+ T follicular helper cells, GzmB+CD4+ and GzmB+CD8+ cytotoxic T cells, and CD69+IFN-γ+TNFα+CD4+ and CD69+IFN-γ+TNFα+CD8+ effector T cells; and (ii) Reduced viral load and COVID-19-like symptoms caused by various VOCs. The combined antigen/LNP-based pan-CoV vaccine could be rapidly adapted for clinical use to confer broader cross-protective immunity against emerging highly mutated and pathogenic VOCs.
1 . A Coronavirus vaccine composition: the Coronavirus vaccine composition comprising a nucleic acid, wherein the nucleic acid comprises a nucleic acid sequence encoding different Coronavirus antigens, wherein the nucleic acid sequence comprises SEQ ID NO: 4 or SEQ ID NO: 5, the nucleic acid sequence comprises SEQ ID NO: 10, and the nucleic acid sequence comprises SEQ ID NO: 7 or SEQ ID NO: 8; or the Coronavirus vaccine composition comprising different proteins wherein the different proteins are different Coronavirus antigens, wherein the different Coronavirus antigens comprise a Coronavirus NSP14 protein encoded by SEQ ID NO: 4 or SEQ ID NO: 5, a Coronavirus Spike protein encoded by SEQ ID NO: 10, and a Coronavirus Nucleoprotein encoded by SEQ ID NO: 7 or SEQ ID NO: 8; and wherein the sequence nucleic acid or different proteins are formulated in a lipid nanoparticle comprising a cationic lipid, a PEG-modified lipid, a sterol, and a non-cationic lipid.
2 . The Coronavirus vaccine composition of claim 1 , wherein the cationic lipid is an ionizable cationic lipid, the non-cationic lipid is a neutral lipid, and the sterol is a cholesterol.
3 . The Coronavirus vaccine composition of claim 2 , wherein the cationic lipid is selected from 2,2-dilinoleyl-4-dimethylaminoethyl-[1,3]-dioxolane, dilinoleyl-methyl-4-dimethylaminobutyrate, or di((Z)-non-2-en-1-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate.
4 . The Coronavirus vaccine composition of claim 1 , wherein: the nucleic acid sequence comprises SEQ ID NO: 4 or SEQ ID NO: 5, the nucleic acid sequence comprises SEQ ID NO: 10, the nucleic acid sequence comprises SEQ ID NO: 7 or SEQ ID NO: 8, and the nucleic acid sequence comprises SEQ ID NO: 1 or SEQ ID NO: 2; and wherein the different proteins are different Coronavirus antigens, wherein the different Coronavirus antigens comprise the Coronavirus NSP14 protein encoded by SEQ ID NO: 4 or SEQ ID NO: 5, the Coronavirus Spike protein encoded by SEQ ID NO: 10, a Coronavirus NSP2 protein encoded by SEQ ID NO: 1 or SEQ ID NO: 2, and the Coronavirus Nucleoprotein encoded by SEQ ID NO: 7 or SEQ ID NO: 8.
5 . A Coronavirus recombinant vaccine composition comprising a pharmaceutical carrier, an adjuvant, and a delivery system;
wherein the delivery system comprises an adeno-associated viral vector based antigen delivery system, wherein the adeno-associated viral vector is an adeno-associated virus vector type 8 (AAV8) serotype or an adeno-associated virus vector type 9 (AAV9) serotype; and
wherein the adeno-associated viral vector comprises a nucleic acid sequence encoding different Coronavirus antigens, wherein the nucleic acid sequence comprises SEQ ID NO: 4 or SEQ ID NO:5, the nucleic acid sequence comprises SEQ ID NO: 10, and the nucleic acid sequence comprises SEQ ID NO:7 or SEQ ID NO:8.
6 . The Coronavirus recombinant vaccine composition of claim 5 , wherein the nucleic acid sequence comprises SEQ ID NO:4 or SEQ ID NO:5, the nucleic acid sequence comprises SEQ ID NO:10, the nucleic acid sequence comprises SEQ ID NO:7 or SEQ ID NO:8, and the nucleic acid sequence comprises SEQ ID NO:1 or SEQ ID NO:2.
7 . The Coronavirus recombinant vaccine composition of claim 5 , wherein the adeno-associated viral vector is an AAV8 serotype.
8 . The Coronavirus recombinant vaccine composition of claim 5 , wherein the adeno-associated viral vector is an AAV9 serotype.
9 . A composition, comprising:
a messenger ribonucleic acid (mRNA) comprising an open reading frame encoding a single Coronavirus NSP14 protein encoded by SEQ ID NO:4 or SEQ ID NO: 5;
an mRNA comprising an open reading frame encoding a single Coronavirus Nucleoprotein encoded by SEQ ID NO:7 or SEQ ID NO: 8; and
an mRNA comprising an open reading frame encoding a single Coronavirus Spike protein encoded by SEQ ID NO: 10;
wherein the mRNAs are formulated in a lipid nanoparticle, and
wherein the lipid nanoparticle comprises a cationic lipid, a PEG-modified lipid, a sterol, and a non-cationic lipid.
10 . The composition of claim 9 , wherein each of the mRNAs further comprise a 5′ untranslated region (UTR) and a 3′ UTR.
11 . The composition of claim 10 , wherein each of the mRNAs further comprise a poly(A) tail and a 5′ cap.
12 . A pharmaceutical composition comprising a first lipid nanoparticle and a second lipid nanoparticle,
wherein each lipid nanoparticle comprises a cationic lipid, a PEG-modified lipid, a sterol, and a non-cationic lipid,
wherein the first lipid nanoparticle comprises a first messenger ribonucleic acid (mRNA) encapsulated therein, a second mRNA encapsulated therein, and a third mRNA encapsulated therein,
wherein the first mRNA comprises an open reading frame encoding a single Coronavirus NSP2 protein encoded by SEQ ID NO: 1 or SEQ ID NO:2,
wherein the second mRNA comprises an open reading frame encoding a single Coronavirus NSP14 protein encoded by SEQ ID NO:4 or SEQ ID NO:5,
wherein the third mRNA comprises an open reading frame encoding a single Coronavirus Nucleoprotein encoded by SEQ ID NO:7 or SEQ ID NO:8, and
wherein the second lipid nanoparticle comprises an mRNA encapsulated therein, wherein the mRNA comprises an open reading frame encoding a single Coronavirus Spike protein encoded by SEQ ID NO:10.
13 . The pharmaceutical composition of claim 12 , wherein each mRNA further comprises a 5′ untranslated region (UTR) and a 3′ UTR.
14 . The pharmaceutical composition of claim 13 , wherein each mRNA further comprises a poly(A) tail and a 5′ cap.
15 . The composition of claim 9 , comprising: the mRNA comprising the open reading frame encoding the single Coronavirus NSP14 protein encoded by SEQ ID NO: 4 or SEQ ID NO: 5; an mRNA comprising an open reading frame encoding a single Coronavirus NSP2 protein encoded by SEQ ID NO: 1 or SEQ ID NO: 2; the mRNA comprising the open reading frame encoding the single Coronavirus Nucleoprotein encoded by SEQ ID NO: 7 or SEQ ID NO: 8; and the mRNA comprising the open reading frame encoding the single Coronavirus Spike protein encoded by SEQ ID NO: 10; wherein the mRNAs are formulated in the lipid nanoparticle, and wherein the lipid nanoparticle comprises the cationic lipid, the PEG-modified lipid, the sterol, and the non-cationic lipid.