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US-20260124294-A1 - IMMUNOGENIC COMPOSITIONS AGAINST THE OMICRON VARIANT OF SEVERE ACUTE RESPITORY SYNDROME CORONAVIRUS 2 (SARS-COV-2)

US20260124294A1US 20260124294 A1US20260124294 A1US 20260124294A1US-20260124294-A1

Abstract

The present invention relates to immunogenic compositions against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially to immunogenic compositions having recombinant SARS-CoV-2 S proteins derived from Omicron subvariants.

Inventors

  • Charles Chen
  • Tsun-Yung Kuo
  • Chung-Chin Wu
  • Wei-Hsuan Tang
  • Chia-En Lien
  • Yi-Jiun Lin

Assignees

  • MEDIGEN VACCINE BIOLOGICS CORPORATION
  • DYNAVAX TECHNOLOGIES CORPORATION

Dates

Publication Date
20260507
Application Date
20231009

Claims (20)

  1. 1 . An immunogenic composition against a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), comprising an antigenic recombinant protein and an adjuvant selected from the group consisting of an aluminum-containing adjuvant, an unmethylated cytosine-phosphate-guanosine (CpG) motif, and a combination thereof, wherein the antigenic recombinant protein substantially consisting of an S1 subunit and an S2 subunit without a transmembrane domain (TM) and a cytoplasmic tail (CT) of spike protein of a SARS-CoV-2 Omicron subvariant at a N-terminus, with a “GSAS” substitution at an S1/S2 cleavage site (S1/S2) and two proline substitutions at a junction between a heptad repeat 1 (HR1) and a central helix (CH), and a C-terminal T4 fibritin trimerization motif of SEQ ID NO: 2, with or without a cleaved HRV3C protease cleavage sequence of SEQ ID NO: 19 at a C-terminus, and wherein the spike protein of a SARS-CoV-2 Omicron subvariant comprises at least the following common mutations compared to spike protein of SARS-CoV-2 Wuhan strain (SEQ ID NO: 42): G142D, S373P, S375F, K417N, N440K, S477N, T478K, E484A, Q498R, N501Y, Y505H, D614G, H655Y, N679K, P681H, N764K, D796Y, Q954H, and N969K.
  2. 2 . The immunogenic composition of claim 1 , wherein the antigenic recombinant protein is at least 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 44 or 45.
  3. 3 . The immunogenic composition of claim 1 , wherein the antigenic recombinant protein is at least one selected from the group consisting of an S-2P Omicron BA.1 recombinant protein comprising an amino acid sequence at least 98%, 99%, or 100% identical to SEQ ID NO: 14 or 15; an S-2P Omicron BA.4/BA.5 recombinant protein comprising an amino acid sequence at least 98%, 99%, or 100% identical to SEQ ID NO: 17 or 18; an S-2P Omicron BA.2.75 recombinant protein comprising an amino acid sequence at least-98%, 99%, or 100% identical to SEQ ID NO: 20 or 21: an S-2P Omicron BA.2 recombinant protein comprising an amino acid sequence at least 98%, 99%, or 100% identical to SEQ ID NO: 22 or 23; an S-2P Omicron BA.4.6 recombinant protein comprising an amino acid sequence at least 98%, 99%, or 100% identical to SEQ ID NO: 24 or 25; an S-2P Omicron BF.7 recombinant protein comprising an amino acid sequence at least 98%, 99%, or 100% identical to SEQ ID NO: 26 or 27; an S-2P Omicron BQ.1 recombinant protein comprising an amino acid sequence at least 98%, 99%, or 100% identical to SEQ ID NO: 28 or 29; an S-2P Omicron BQ.1.1 recombinant protein comprising an amino acid sequence at least 98%, 99%, or 100% identical to SEQ ID NO: 30 or 31; an S-2P Omicron XBB.1.5 recombinant protein comprising an amino acid sequence at least 98%, 99%, or 100% identical to SEQ ID NO: 32 or 33; an S-2P Omicron XBB.1 recombinant protein comprising an amino acid sequence at least 98%, 99%, or 100% identical to SEQ ID NO: 34 or 35; an S-2P Omicron XBB.1.16 recombinant protein comprising an amino acid sequence at least 98%, 99%, or 100% identical to SEQ ID NO: 36 or 37: an S-2P Omicron BA.2.86 recombinant protein comprising an amino acid sequence at least 98%, 99%, or 100% identical to SEQ ID NO: 38 or 39; and an S-2P Omicron EG.5.1 recombinant protein comprising an amino acid sequence at least 98%, 99%, or 100% identical to SEQ ID NO: 40 or 41.
  4. 4 . The immunogenic composition of claim 1 , further comprising an S-2P W recombinant protein, substantially consisting of residues 14-1208 of spike protein of SARS-CoV-2 Wuhan strain with proline substitutions at residues 986 and 987 and a “GSAS” substitution at residues 682-685 and a C-terminal T4 fibritin trimerization motif of SEQ ID NO: 2, with or without a cleaved HRV3C protease cleavage sequence of SEQ ID NO: 19 at a C-terminus.
  5. 5 . The immunogenic composition of claim 4 , wherein the S-2P W recombinant protein comprises an amino acid sequence at least 98%, 99%, or 100% identical to SEQ ID NO: 5 or 6.
  6. 6 . The immunogenic composition of claim 1 , wherein the aluminum-containing adjuvant comprises aluminum hydroxide, aluminum oxyhydroxide, aluminum hydroxide gel, aluminum phosphate, aluminum phosphate gel, aluminum hydroxyphosphate, aluminum hydroxyphosphate sulfate, amorphous aluminum hydroxyphosphate sulfate, potassium aluminum sulfate, aluminum monostearate or a combination thereof.
  7. 7 . The immunogenic composition of claim 6 , wherein a 0.5 ml dose of the immunogenic composition comprises from about 250 to about 1500 μg Al 3+ , or about 375 μg Al 3+ or about 750 μg Al 3+ .
  8. 8 . The immunogenic composition of claim 1 , wherein the unmethylated CpG motif comprises a synthetic oligodeoxynucleotide (ODN) of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, or a combination thereof.
  9. 9 . The immunogenic composition of claim 8 , wherein a 0.5 ml dose of the immunogenic composition comprises from about 750 to about 3000 μg of the synthetic oligodeoxynucleotide, or about 750 μg, 1500 μg, or 3000 μg of the synthetic oligodeoxynucleotide.
  10. 10 . A method for eliciting an immune response against a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a subject in need thereof, comprising administering to the subject at least one dose of the immunogenic composition of claim 1 .
  11. 11 . The method of claim 10 , wherein the subject was administered with at least one dose of an immunogenic composition derived from SARS-CoV-2 Wuhan strain before the administration with the at least one dose of the immunogenic composition of claim 1 .
  12. 12 . The method of claim 11 , wherein the immunogenic composition derived from SARS-CoV-2 Wuhan strain comprises a polynucleotide encoding at least a fragment of spike protein of SARS-CoV-2 Wuhan strain or a polypeptide of at least a fragment of spike protein of SARS-CoV-2 Wuhan strain.
  13. 13 . The method of claim 12 , wherein the at least a fragment of spike protein of SARS-CoV-2 Wuhan strain comprises a polypeptide sequence at least 98%, 99%, or 100% identical to SEQ ID NO: 5 or 6.
  14. 14 . The method of claim 11 , wherein the immunogenic composition derived from SARS-CoV-2 Wuhan strain comprises a polypeptide sequence at least 98%, 99%, or 100% identical to SEQ ID NO: 5 or 6, and an adjuvant selected from the group consisting of an aluminum-containing adjuvant, an unmethylated cytosine-phosphate-guanosine (CpG) motif, and a combination thereof.
  15. 15 . The method of claim 14 , wherein the aluminum-containing adjuvant comprises aluminum hydroxide, aluminum oxyhydroxide, aluminum hydroxide gel, aluminum phosphate, aluminum phosphate gel, aluminum hydroxyphosphate, aluminum hydroxyphosphate sulfate, amorphous aluminum hydroxyphosphate sulfate, potassium aluminum sulfate, aluminum monostearate or a combination thereof.
  16. 16 . The method of claim 15 , wherein a 0.5 ml dose of the immunogenic composition comprises from about 250 to about 1500 μg Al 3+ , or about 375 μg Al + or about 750 μg Al 3+ .
  17. 17 . The method of claim 14 , wherein the unmethylated CpG motif comprises a synthetic oligodeoxynucleotide (ODN) of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, or a combination thereof.
  18. 18 . The method of claim 17 , wherein a 0.5 ml dose of the immunogenic composition comprises from about 750 to about 3000 μg of the synthetic oligodeoxynucleotide, or about 750 μg, 1500 μg, or 3000 μg of the synthetic oligodeoxynucleotide.
  19. 19 . The method of claim 11 , wherein the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an Omicron variant.
  20. 20 . The method of claim 11 , wherein the immunogenic composition is administered by intramuscular injection.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to and the benefit of U.S. Provisional Application No. 63/414,042, filed on Oct. 7, 2022, the disclosure of which is incorporated by reference in its entirety. SUBMISSION OF SEQUENCE LISTING AS ASCII TEXT FILE This application includes an electronically submitted sequence listing in XML format. The XML file contains a sequence listing entitled “Omicron S-2P Sequence Listing.xml” which was created on Oct. 6, 2023 and is 82,878 bytes in size. The sequence listing contained in this XML file is part of the specification and is hereby incorporated by reference herein in its entirety. BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to immunogenic compositions against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially to immunogenic compositions having recombinant SARS-CoV-2 S proteins derived from Omicron subvariants. 2. Description of the Prior Art On 31 Dec. 2019, the World Health Organization (WHO) was alerted to several cases of pneumonia in Wuhan City, Hubei Province of China. The viral pathogen did not match any other known virus and was later officially named “severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).” The official name of the disease caused by SARS-CoV-2 is coronavirus disease 2019 (COVID-19). Common symptoms of COVID-19 include fever, dry cough, fatigue, tiredness, muscle or body aches, sore throat, diarrhea, conjunctivitis, headache, loss of taste or smell, a rash on skin, and shortness of breath. While the majority of cases result in mild symptoms, some progress to acute respiratory distress syndrome (ARDS), precipitated by cytokine storm, multi-organ failure, septic shock, and blood clots. The first confirmed death from the coronavirus infection occurred on Jan. 9, 2020, and as of Sep. 4, 2023, 770,563.467 confirmed cases of COVID-19, including 6,957,216 deaths, have been reported to the WHO (WHO Coronavirus (COVID-19) Dashboard, https://covid19.who.int). The numbers are still growing fast. Since the beginning of the COVID-19 pandemic, mutants have been detected periodically. A number of them were found to carry mutations in the crucial receptor-binding domain (RBD), a prime target for antibody recognition and neutralization. Among these variants, the newly emerged Omicron (B.1.1.529) variant has 32 changes in its spike protein relative to that of the original virus (Wuhan-hu-1), particularly in RBD and the N-terminal domain, the primary targets of neutralizing antibodies. In just a few weeks since the discovery of Omicron variant, it has turned out to be highly transmissible and less susceptible to vaccines than other variants. The Omicron variant and its subvariants have spread fast around the world and been identified in more than 110 countries. Therefore, vaccines that are effective against the Omicron variant of SARS-CoV-2 are urgently needed. SUMMARY OF THE INVENTION In one aspect, the present invention provides immunogenic compositions against a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), comprising an antigenic recombinant protein and an adjuvant selected from the group consisting of an aluminum-containing adjuvant, an unmethylated cytosine-phosphate-guanosine (CpG) motif, and a combination thereof, wherein the antigenic recombinant protein comprises a recombinant protein derived from the spike protein of SARS-CoV-2 Omicron subvariants. In some embodiments, the immunogenic composition described herein provides one or more of improved immunogenicity, an enhanced immune response, and/or broad-spectrum immunity. In other embodiments, methods, formulations, articles, devices, and/or preparations for administering the immunogenic composition described herein, which provides improved immunogenicity, an enhanced immune response, and/or a broad-spectrum immunity, to a subject are also disclosed. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following embodiments. Embodiment 1. An immunogenic composition against a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), comprising an antigenic recombinant protein and an adjuvant selected from the group consisting of an aluminum-containing adjuvant, an unmethylated cytosine-phosphate-guanosine (CpG) motif, and a combination thereof, wherein the antigenic recombinant protein substantially consisting of an S1 subunit and an S2 subunit without a transmembrane domain (TM) and a cytoplasmic tail (CT) of spike protein of a SARS-CoV-2 Omicron subvariant at a N-terminus, with a “GSAS” substitution at an S1/S2 cleavage site (S1/S2) and two proline substitutions at a junction between a heptad repeat 1 (HR1) and a central helix (CH), and a C-terminal T4 fibritin trimerization motif of SEQ ID NO: 2,