Replication-competent attenuated chimeric VSV vectors encoding immunogenic SARS-CoV-2 spike proteins

A recombinant VSV particle comprising a replication-competent attenuated chimeric VSV vector comprising:

• a) at least a portion of a VSV genome comprising a VSV-N gene, VSV-P gene, VSV-M gene, and VSV-L gene and
• b) a nucleic acid sequence encoding an immunogenic variant of a SARS-CoV-2 S protein;
• wherein
• (i) the nucleic acid sequence encoding the immunogenic variant of the SARS-CoV-2 S protein replaces all of the VSV-G gene in the VSV genome or all of the VSV-G gene in the VSV genome except for a portion of the VSV-G gene encoding a VSV-G protein cytoplasmic tail and/or a portion of the VSV-G gene encoding VSV-G transmembrane domain, and
• (ii) the immunogenic variant of the SARS-CoV-2 S protein has at least 97% sequence identity over its own length to any one of SEQ ID NOS:
• 1, 4, 7, 10, 13, 16, 19, 22, 25-67, 153, or 158;
• and
• (iii) the immunogenic variant of the SARS-CoV-2 S protein comprises a C-terminal deletion;
• and
• (iv) the immunogenic variant of the SARS-CoV-2 S protein comprises one or more mutations relative to SEQ ID NO:
• 1, wherein the one or more mutations are chosen from:
• i) H655Y, R682K, and R685G;
• ii) H655Y, R682K, R685G, and a deletion of the 9 amino acids (Δ9) at the C-terminal end of the amino acid sequence of SEQ ID NO:
• 1;
• iii) H655Y, R682K, R685G, and a deletion of the 13 amino acids (Δ13) at the C-terminal end of the amino acid sequence of SEQ ID NO:
• 1;
• iv) Q321P, H655Y, T6781, and P812R;
• v) Q321P, H655Y, T678I, P812R, and a deletion of the 23 amino acids (Δ23) at the C-terminal end of the amino acid sequence of SEQ ID NO:
• 1;
• vi) E154D, S115L, T678I, R685G, and M1233K;
• vii) R685G, S813R, and a deletion of the 9 amino acids (Δ9) at the C-terminal end of the amino acid sequence of SEQ ID NO:
• 1;
• viii) H655Y, R682K, and a deletion of the 13 amino acids (Δ13) at the C-terminal end of the amino acid sequence of SEQ ID NO:
• 1;
• ix) R685G, S813F, and a deletion of the 9 amino acids (Δ9) at the C-terminal end of the amino acid sequence of SEQ ID NO:
• 1;
• x) R683G, S813F and a deletion of the 23 amino acids (Δ23) at the C-terminal end of the amino acid sequence of SEQ ID NO:
• 1;
• xi) R683G, S813F, R685G, and a deletion of 23 amino acids (Δ23) at the C-terminal end of the amino acid sequence of SEQ ID NO:
• 1;
• xii) H655Y, P681S, R682K, and a deletion of the 13 amino acids (Δ13) at the C-terminal end of the amino acid sequence of SEQ ID NO:
• 1;
• xiii) R683G and a deletion of the 23 amino acids (Δ23) at the C-terminal end of the amino acid sequence of SEQ ID NO:
• 1;
• xiv) H655Y and a deletion of the 23 amino acids (Δ23) at the C-terminal end of the amino acid sequence of SEQ ID NO:
• 1;
• xv) R683G, D1118A, and a deletion of the 23 amino acids (Δ23) at the C-terminal end of the amino acid sequence of SEQ ID NO:
• 1;
• xvi) R683G, N715S, and a deletion of the 23 amino acids (Δ23) at the C-terminal end of the amino acid sequence of SEQ ID NO:
• 1;
• xvii) H655Y, N709S, and a deletion of the 13 amino acids (Δ13) at the C-terminal end of the amino acid sequence of SEQ ID NO:
• 1;
• xviii) F140V, H655Y, and a deletion of the 23 amino acids (Δ23) at the C-terminal end of the amino acid sequence of SEQ ID NO:
• 1;
• xix) a deletion of the 21 amino acids (Δ21) at the C-terminal end of the amino acid sequence of SEQ ID NO:
• 1;
• xx) a deletion of the 19 amino acids (Δ19) at the C-terminal end of the amino acid sequence of SEQ ID NO:
• 1;
• xxi) E484D, H655Y, and a deletion of 21 amino acids (Δ21) at the C-terminal end of the amino acid sequence of SEQ ID NO:
• 1;
• xxii) H665Y, R685G and a deletion of the 19 amino acids (Δ19) at the C-terminal end of the amino acid sequence of SEQ ID NO:
• 1, wherein the SARS-CoV-2 S protein further comprises a fragment of at least 21 amino acids at the C-terminal end of a VSV-G protein;
• xxiii) D614G;
• and
• xxiv) D614N.