LARGE SEQUENCE PAN-CORONAVIRUS VACCINE COMPOSITIONS
Pan-coronavirus vaccines for inducing efficient, powerful and long-lasting protection against all Coronaviruses infections and diseases, comprising multiple highly conserved large sequences which may comprise one or more conserved B, CD4 and CD8 T cell epitopes that help provide multiple targets for the body to develop an immune response for preventing a Coronavirus infection and/or disease. In certain embodiments, the large sequences are conserved proteins or large sequences, e.g., sequences that are highly conserved among human coronaviruses and/or animal coronaviruses (e.g., coronaviruses isolated from animals susceptible to coronavirus infections).
1 . A universal pre-emptive pan-Coronavirus vaccine composition, the composition comprising one or more large sequences, wherein the one or more large sequences comprise at least one of:
a) one or more conserved coronavirus B-cell target epitopes;
b) one or more conserved coronavirus CD4 + T cell target epitopes; and/or
c) one or more conserved coronavirus CD8 + T cell target epitopes;
wherein at least one epitope is derived from a non-spike protein.
2 . The composition of claim 1 , wherein the non-spike proteins are encoded by ORF1ab, ORF3a, ORF6, ORF7a, ORF7b, ORF8, or ORF10, or derived from an Envelope protein, a Membrane protein, or a Nucleocapsid protein.
3 . The composition of claim 1 , wherein at least one large sequence is highly conserved among human and animal Coronaviruses.
4 . The composition of claim 1 , wherein the one large sequence is derived from one or more of: one or more SARS-CoV-2 human strains or variants in current circulation; one or more SARS-CoV-2 variants identified in the future; one or more coronaviruses that has caused a previous human outbreak; one or more coronaviruses isolated from animals selected from a group consisting of bats, pangolins, civet cats, minks, camels, and other animal receptive to coronaviruses; or one or more coronaviruses that cause the common cold, past, current, and future coronavirus outbreaks.
5 . The composition of claim 4 , wherein the one or more SARS-CoV-2 human strains or variants in current circulation are selected from: variant B.1.177; variant B.1.160, variant B.1.1.7 (UK), variant P.1 (Japan/Brazil), variant B.1.351 (South Africa), variant B.1.427 (California), variant B.1.429 (California), variant B.1.258; variant B.1.221; variant B.1.367; variant B.1.1.277; variant B.1.1.302; variant B.1.525; variant B.1.526, variant S:677H; variant S:677P; B.1.617.2-Delta, variant B.1.1.529-Omicron (BA.1); sub-variant Omicron (BA.1); sub-variant Omicron (BA.2); sub-variant Omicron (BA.3); sub-variant Omicron (BA.4); sub-variant Omicron (BA.5).
6 . The composition of claim 4 , wherein the one or more coronaviruses that cause the common cold are selected from: 229E alpha coronavirus, NL63 alpha coronavirus, OC43 beta coronavirus, and HKU1 beta coronavirus.
7 . The composition of claim 1 , wherein at least one large sequence is a whole protein sequence expressed by SARS-CoV-2, a partial protein sequence expressed by SARS-CoV-2, or a combination thereof.
8 . The composition of claim 7 , wherein the whole protein sequence or the partial protein sequence expressed by SAR-CoV-2 is selected from SEQ ID NO: 182-193, SEQ ID NO: 148-159, SEQ ID NO: 360-383, and SEQ ID NO: 348-359.
9 . The composition of claim 1 further comprising a T cell attracting chemokine, wherein the T cell attracting chemokine is CCL5, CXCL9, CXCL10, CXCL11, or a combination thereof.
10 . The composition of claim 1 further comprising a composition that promotes T cell proliferation and T-cell memory, wherein the composition promotes T cell proliferation and memory is IL-7, IL-2, or IL-15.
11 . The composition of claim 1 , wherein the composition comprises any of SEQ ID NO: 139-147 and SEQ ID NO: 295-347.
12 . The composition of claim 1 , wherein the vaccine composition protects against disease caused by one or more coronavirus variants or coronavirus subvariants.
13 . The composition of claim 12 , wherein the coronavirus variants or coronavirus subvariants comprise past or currently circulating coronavirus variants or coronavirus subvariants wherein the coronavirus variants comprise alpha, beta, gamma, delta, and omicron.
14 . The composition of claim 12 , wherein the coronavirus variants or coronavirus subvariants comprise future variants or future subvariants of human and animal coronavirus.
15 . The composition of claim 1 , wherein the vaccine composition protects against infection and re-infection of coronavirus variants or coronavirus subvariants.
16 . The composition of claim 15 , wherein the coronavirus variants or coronavirus subvariants comprise past or currently circulating coronavirus variants or coronavirus subvariants, wherein the coronavirus variants comprise alpha, beta, gamma, delta, and omicron.
17 . The composition of claim 15 , wherein the coronavirus variants or coronavirus subvariants comprise future variants or future subvariants of human and animal coronavirus.
18 . The composition of claim 15 , wherein the vaccine composition protects against infection or reinfection of one or more coronavirus variants or coronavirus subvariant.
19 . The composition of claim 18 , wherein the vaccine composition protects against infection or reinfection of multiple coronavirus variants or coronavirus subvariants.
20 . The composition of claim 18 , wherein the vaccine composition protects against infection or re-infection of one coronavirus variants or coronavirus subvariants.
21 . The composition of claim 1 , wherein the vaccine composition induces strong and long-lasting protection mediated by antibodies (Abs), CD4+ T helper (Th1) cells, and/or CD8+ cytotoxic T-cells.
22 . The composition of claim 1 , wherein the composition protects against Sarbecoviruses, wherein sarbecoviruses comprise SARS-CoV1 or SARS-CoV2.