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EP-4735035-A2 - SARS-COV-2 RNA VACCINES AND USES THEREOF

EP4735035A2EP 4735035 A2EP4735035 A2EP 4735035A2EP-4735035-A2

Abstract

The present disclosure relates to SARS-CoV-2 RNA vaccines and uses thereof. The present disclosure also relates to conventional mRNA vaccines and self-replicating RNA vaccines for the treatment of a SARS-CoV-2 infection or COVID-19.

Inventors

  • CHANG, CHENG
  • Cai, Yongfei

Assignees

  • Seqirus Inc.

Dates

Publication Date
20260506
Application Date
20240627

Claims (20)

  1. 1. A self-replicating RNA comprising a nucleotide sequence encoding an antigen operably linked to a regulatory element, wherein the antigen is a spike (S) protein from the omicron strain of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
  2. 2. The self-replicating RNA of claim 1, further comprising a nucleotide sequence encoding a second antigen operably linked to a regulatory element.
  3. 3. The self-replicating RNA of claim 2, wherein the second antigen is a nucleocapsid (N) protein from a SARS-CoV-2.
  4. 4. The self-replicating RNA of claim 3, wherein the N protein is from the omicron strain of a SARS-CoV-2.
  5. 5. The self-replicating RNA of claim 1, wherein the regulatory element is selected from the group consisting of a SG promoter and an IRES.
  6. 6. The self-replicating RNA of claim 2, wherein the self-replicating RNA comprises in 5’ to 3’ order: a) the nucleotide sequence encoding an S protein antigen from the omicron strain of a SARS-CoV-2; and b) the nucleotide sequence encoding an N protein antigen from a SARS-CoV-2.
  7. 7. The self-replicating RNA of claim 2, wherein the self-replicating RNA comprises in 5’ to 3’ order: a) the nucleotide sequence encoding an N protein antigen from a SARS-CoV-2; and b) the nucleotide sequence encoding an S protein antigen from the omicron strain of a SARS-CoV-2.
  8. 8. The self-replicating RNA of claim 2, wherein the self-replicating RNA comprises in 5’ to 3’ order: a) the nucleotide sequence encoding an S protein antigen from the omicron strain of a SARS-CoV-2 operably linked to a SG promoter; and b) the nucleotide sequence encoding an N protein antigen from a SARS-CoV-2 operably linked to a regulatory element selected from the group consisting of a SG promoter and an internal ribosome entry site (IRES), optionally encoded by the sequence set forth in SEQ ID NO: 18
  9. 9. The self-replicating RNA of claim 2, wherein the self-replicating RNA comprises in 5’ to 3’ order: a) the nucleotide sequence encoding an N protein antigen from a SARS-CoV-2 operably linked to a SG promoter; and b) the nucleotide sequence encoding an S protein antigen from the omicron strain of a SARS-CoV-2 operably linked to a regulatory element selected from the group consisting of a SG promoter and an internal ribosome entry site (IRES), optionally encoded by the sequence set forth in SEQ ID NO: 19.
  10. 10. The self-replicating RNA of claim 2, wherein the N protein is from the delta, beta, alpha, gamma or 2019-nCoV/USA-WAl/2020 strain of SARS-CoV-2.
  11. 11. The self-replicating RNA of claim 1, wherein the self-replicating RNA is a monocistronic self-replicating RNA.
  12. 12. The self-replicating RNA of claim 2, wherein the self-replicating RNA is a polycistronic self-replicating RNA.
  13. 13. The self-replicating RNA of claim 2, wherein the regulatory element is the same as the regulatory element of claim 1.
  14. 14. The self-replicating RNA of claim 1, wherein the regulatory element is a promoter, an internal ribosome entry site (IRES) or a Kozak consensus sequence or a combination thereof.
  15. 15. The self-replicating RNA of claim 14, wherein the promoter is a subgenomic (SG) promoter.
  16. 16. The self-replicating RNA of claim 14, wherein the SG promoter is a minimal SG promoter or an extended SG promoter.
  17. 17. The self-replicaing RNA of claim 16, wherein the extended SG promoter is extended at the 5’ end with nucleotides occurring in a sequence encoding a non- structural protein of an RNA virus.
  18. 18. The self-replicaing RNA of claim 16, wherein the minimal SG promoter is encoded by a sequence set forth in SEQ ID NO: 1.
  19. 19. The self-replicaing RNA of claim 16, wherein the extended SG promoter is encoded by a sequence set forth in SEQ ID NO: 5.
  20. 20. The self-replicating RNA of claim 2, wherein the nucleotide sequence encoding a second antigen is operably linked to an IRES, optionally located 3’ to the nucleotide sequence encoding a second antigen.

Description

SARS-CoV-2 RNA VACCINES AND USES THEREOF RELATED APPLICATION DATA The present application claims priority from United States Patent Application No. 63/511,340 filed 30 June 2023 entitled “SARS-CoV-2 RNA vaccines and uses thereof’, the entire contents of which is hereby incorporated by reference. SEQUENCE LISTING The present application is filed together with a Sequence Listing in electronic form. The entire contents of the Sequence Listing are hereby incorporated by reference. FIELD The present disclosure relates to SARS-CoV-2 RNA vaccines and uses thereof. The present disclosure also relates to conventional mRNA vaccines and self-replicating RNA vaccines for the treatment of a SARS-CoV-2 infection or COVID-19. BACKGROUND Respiratory viral infections are a significant threat to human health and lives. Infections such as those caused by the influenza virus and severe acute respiratory syndrome coronavirus (SARS-CoV) have been known to cause global pandemics, killing millions of people worldwide. More recently, SARS-CoV-2 has been responsible for causing the worldwide pandemic of the severely infectious coronavirus disease 2019 (COVID-19). SARS-CoV-2, belonging to the family Coronaviridae and the subfamily orthocoronaviruses, is an enveloped single-stranded positive-strand RNA virus which encodes non- structural proteins that play roles in viral replication and translation, and structural proteins including the spike protein (S protein), membrane protein (M protein), envelope protein (E protein) and nucleocapsid protein (N protein). The S protein is a transmembrane glycoprotein forming prominent homotrimers on the surface of the virus, consisting of two functional subunits SI and S2 which have become the main targets for current genetic engineering vaccine development. SARS-CoV-2 has a high propensity to mutate, with a significant number of mutant strains now identified globally. The predominant mutant strains include: the Alpha (B.1.1.7) mutant, the Beta (B.1.351) mutant, the Gamma (Pl) mutant, the Epsilon (B.1.429) mutant, the Delta (B.1.617.2) mutant, the Kappa (B.1.617.1) mutant and the Omicron (B.1.1.529) mutant, which vary in their transmissibility, pathogenicity, and/or immune escape capabilities. Typically, these mutant strains are identified based on the number and location of mutations in the viral genome, specifically in the genome encoding the S protein of the mutant SARS-CoV-2. The Omicron strain contains up to 36 amino acid mutation sites and this strain in particular has been shown to have an improved affinity for the ACE2 target receptor, thereby enhancing its toxicity and infectivity, and accelerating virus escape. There are currently few vaccines available that target specific strains of SARS-CoV-2 such as the Omicron strain. Currently available vaccines, such as those developed against the Wuhan (original) strain, which are not specifically targeted to evolving mutant strains, are known to provide for a reduced protective effect and/or immunogenicity. There is therefore a need for the development of new vaccines that can specifically target SARS-CoV-2 strains, such as the omicron strain of SARS-CoV-2. SUMMARY The present disclosure is based on the inventors’ identification of a RNA comprising an antigen from a severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) virus that is suitable for the treatment of a SARS-Cov-2 infection or coronavirus disease 2019 (COVID-19). In particular, the findings by the inventors provide basis for a RNA comprising an antigen from a SARS-CoV-2, for example a spike (S) protein from the omicron strain (or variants thereof) of a SARS-CoV-2, that is suitable for the treatment of a SARS-CoV-2 infection or COVID-19. Furthermore, the findings by the inventors provide basis for methods of treating or preventing or delaying progression of a disease or disorder such as a SARS-CoV-2 infection or COVID-19, as well as complications thereof including pneumonia, sepsis and acute respiratory distress syndrome (ARDS)) in a subject. Accordingly, the present disclosure provides a polynucleotide comprising a nucleotide sequence encoding an antigen operably linked to a regulatory element, wherein the antigen is a spike (S) protein from the omicron strain of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). When discussing an “omicron strain” of SARS-CoV-2 herein, the term will be understood to include variants and sub-lineages arising from an omicron strain of SARS- CoV-2. For example, an omicron strain of SARS-CoV-2 includes BA. l strains, BA.2 strains, XB strains, XBB strains, JN.l strains, JN.2 strains, JN.3 strains, KP.l strains, KP.2 strains. In one example, the polynucleotide comprises a nucleotide sequence at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or identical to the sequence set forth in SEQ ID NO: 17. In one example, the polynucleotide further comprises a nucleotide sequence encoding a second antigen ope