Coronavirus vaccines comprising a tlr9 agonist

Abstract

The present disclosure relates to immunogenic compositions comprising a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen, and a toll-like receptor 9 (TLR9) agonist, such as an oligonucleotide comprising an unmethylated cytidine-phospho-guanosine (CpG) motif. The immunogenic compositions are suitable for stimulating an immune response against a SARS-CoV-2 in an individual in need thereof.

We claim: 
     
         1 . An immunogenic composition for stimulating an immune response against a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), comprising a SARS-CoV-2 antigen and a toll-like receptor 9 (TLR9) agonist, wherein the SARS-CoV-2 antigen comprises a truncated, recombinant spike (S) protein devoid of signal peptide, transmembrane and cytoplasmic domains of a full length S protein, the TLR9 agonist is an oligonucleotide of from 10 to 35 nucleotides in length comprising an unmethylated cytidine-phospho-guanosine (CpG) motif, and the SARS-CoV-2 antigen and the oligonucleotide are present in the immunogenic composition in amounts effective to stimulate an immune response against the SARS-CoV-2 antigen in a mammalian subject. 
     
     
         2 . The composition of  claim 1 , wherein the oligonucleotide comprises the sequence 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 3) 
                 
                     
                   5′-AACGTTCGAG-3′. 
                 
             
                
                
               
            
           
         
       
     
     
         3 . The composition of  claim 1 , wherein the oligonucleotide comprises the sequence of 5′-TGACTGTGAA CGTTCGAGAT GA-3′(SEQ ID NO:1). 
     
     
         4 . The composition of  claim 1 , wherein the oligonucleotide comprises a modified nucleoside, optionally wherein the modified nucleoside is selected from the group consisting of 2′-deoxy-7-deazaguanosine, 2′-deoxy-6-thioguanosine, arabinoguanosine, 2′-deoxy-2′substituted-arabinoguanosine, and 2′-O-substituted-arabinoguanosine. 
     
     
         5 . The composition of  claim 4 , wherein the oligonucleotide comprises the sequence 5′-TCG 1 AACG 1 TTCG 1 -3′ (SEQ ID NO:2) in which G 1  is 2′-deoxy-7-deazaguanosine, optionally wherein the oligonucleotide comprises the sequence 5′-TCG 1 AACG 1 TTCG 1 -X-G 1 CTTG 1 CAAG 1 CT-5′, in which G 1  is 2′-deoxy-7-deazaguanosine and X is glycerol (5′-SEQ ID NO:2-3′-X-3′-SEQ ID NO:2-5′). 
     
     
         6 . The composition of  claim 3 , wherein the oligonucleotide comprises at least one phosphorothioate linkage, or wherein all nucleotide linkages are phosphorothioate linkages. 
     
     
         7 . The composition of  claim 6 , wherein the oligonucleotide is a single-stranded oligodeoxynucleotide. 
     
     
         8 . The composition of  claim 7 , wherein a 0.5 ml dose of the immunogenic composition comprises from about 750 to about 3000 μg of the oligonucleotide, or wherein the immunogenic composition comprises about 750 μg, about 1500 μg, or about 3000 μg of the oligonucleotide. 
     
     
         9 . The composition of  claim 8 , wherein the SARS-CoV-2 antigen comprises a S protein ectodomain without a S1/S2 furin recognition site. 
     
     
         10 . The composition of  claim 9 , wherein the S protein ectodomain comprises the amino acid sequence of residues 14-1208 of SEQ ID NO:6 or the amino acid sequence at least 90%, 95%, 96%, 97%, 98% or 99% to residues 14-1208 of SEQ ID NO:6. 
     
     
         11 . The composition of  claim 10 , wherein the SARS-CoV-2 antigen is a fusion protein comprising a C-terminal trimerization domain. 
     
     
         12 . The composition of  claim 11 , wherein the trimerization domain is a T4 fibritin trimerization domain, optionally comprising the amino acid sequence of SEQ ID NO:10 or the amino acid sequence at least 90%, 95%, 96%, 97%, 98% or 99% to SEQ ID NO:10. 
     
     
         13 . The composition of  claim 3 , wherein the SARS-CoV-2 antigen further comprises one or more of the SARS-CoV-2 membrane (M) protein, nucleocapsid (N) protein, and envelope (E) protein. 
     
     
         14 . The composition of any one of  claims 1 - 13 , further comprising an aluminum salt adjuvant. 
     
     
         15 . The composition of  claim 14 , wherein the aluminum salt adjuvant comprises one or more of the group consisting of amorphous aluminum hydroxyphosphate sulfate, aluminum hydroxide, aluminum phosphate, and potassium aluminum sulfate. 
     
     
         16 . The composition of  claim 14 , wherein the aluminum salt adjuvant comprises aluminum hydroxide. 
     
     
         17 . The composition of  claim 15 , wherein a 0.5 ml dose of the immunogenic composition comprises from about 0.25 to about 0.50 mg Al 3+ , or about 0.375 mg Al 3+ . 
     
     
         18 . The composition of  claim 17 , wherein the mammalian subject is a human subject. 
     
     
         19 . A kit comprising:
 i) the immunogenic composition of  claim 14 , and   ii) instructions for administration of the composition to stimulate an immune response against the SARS-CoV-2 antigen in the mammalian subject.   
     
     
         20 . The kit of  claim 19 , further comprising iii) a syringe and needle for intramuscular injection of the immunogenic composition. 
     
     
         21 . A method for stimulating an immune response against a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a mammalian subject, comprising administering the immunogenic composition of  claim 14  to a mammalian subject so as to stimulate an immune response against the SARS-CoV-2 antigen in the mammalian subject. 
     
     
         22 . The method of  claim 21 , wherein the mammalian subject is a human subject and/or the immunogenic composition is administered by intramuscular injection. 
     
     
         23 . Use of the immunogenic composition of  claim 14  for stimulating an immune response against a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a mammalian subject, the method comprising administering to the subject an effective amount of the immunogenic composition. 
     
     
         24 . Use of the immunogenic composition of  claim 14  for protecting a mammalian subject from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the method comprising administering to the subject an effective amount of the immunogenic composition. 
     
     
         25 . Use of the immunogenic composition of  claim 14  for preventing a mammalian subject from contracting COVID-19 disease, the method comprising administering to the subject an effective amount of the immunogenic composition. 
     
     
         26 . The use of any one of  claims 23 - 25 , wherein the mammalian subject is a human subject and/or the immunogenic composition is administered by intramuscular injection.