Search

EP-4735034-A2 - COMBINATION RNA VACCINE

EP4735034A2EP 4735034 A2EP4735034 A2EP 4735034A2EP-4735034-A2

Abstract

The present disclosure relates to combination RNA vaccines and uses thereof. The present disclosure also relates to conventional mRNA vaccines and self-replicating RNA vaccines for the treatment of diseases or conditions including respiratory syncytial virus (RSV).

Inventors

  • RAMANATHAN, PALANIAPPAN
  • ADVANI, Vivek

Assignees

  • Seqirus Inc.

Dates

Publication Date
20260506
Application Date
20240628

Claims (20)

  1. 1. A RNA comprising: (a) a nucleotide sequence encoding an antigen from a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); (b) a nucleotide sequence encoding a second antigen from influenza, and (c) a nucleotide sequence encoding a third antigen from a respiratory syncytial virus (RSV), wherein each nucleotide sequence is operably linked to a regulatory element.
  2. 2. The RNA of claim 1, wherein the the RNA comprises, in 5’ to 3’ order: (a) the nucleotide sequence encoding an antigen from a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); (b) the nucleotide sequence encoding an antigen from influenza, and (c) the nucleotide sequence encoding an antigen from a respiratory syncytial virus (RSV).
  3. 3. The RNA of claim 1, wherein the RNA comprises in 5’ to 3’ order: (a) the nucleotide sequence encoding an antigen from a respiratory syncytial virus (RSV); (b) the nucleotide sequence encoding an antigen from a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); and (c) the nucleotide sequence encoding an antigen from influenza.
  4. 4. The RNA of claim 1, wherein the RNA comprises in 5’ to 3’ order: (a) the nucleotide sequence encoding an antigen from influenza; (b) the nucleotide sequence encoding an antigen from a respiratory syncytial virus (RSV); and (c) the nucleotide sequence encoding an antigen from a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
  5. 5. The RNA of claim 1, wherein the regulatory element is selected from the group consisting of a promoter, a Kozak consensus sequence and an IRES.
  6. 6. The RNA of claim 1, wherein the RNA comprises: (a) a nucleotide sequence encoding an antigen from a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), operably linked to a SG promoter; (b) a nucleotide sequence encoding a second antigen from influenza, operably linked to an IRES or a SG promoter, and (c) a nucleotide sequence encoding a third antigen from a respiratory syncytial virus (RSV), operably linked to an IRES or a SG promoter.
  7. 7. The RNA of claim 6, wherein the RNA comprises, in 5’ to 3’ order: (a) a nucleotide sequence encoding an antigen from a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), operably linked to a SG promoter; (b) a nucleotide sequence encoding a second antigen from influenza, operably linked to an IRES or a SG promoter, and (c) a nucleotide sequence encoding a third antigen from a respiratory syncytial virus (RSV), operably linked to an IRES or a SG promoter.
  8. 8. The RNA of claim 6, wherein the RNA comprises, in 5’ to 3’ order: (a) a nucleotide sequence encoding an antigen from a respiratory syncytial virus (RSV), operably linked to a SG promoter; (b) a nucleotide sequence encoding a second antigen from a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), operably linked to an IRES or a SG promoter, and (c) a nucleotide sequence encoding a third antigen from influenza, operably linked to an IRES or a SG promoter.
  9. 9. The RNA of claim 6, wherein the RNA comprises, in 5’ to 3’ order: (a) a nucleotide sequence encoding an antigen from influenza, operably linked to a SG promoter; (b) a nucleotide sequence encoding a second antigen from a respiratory syncytial virus (RSV), operably linked to an IRES or a SG promoter, and (c) a nucleotide sequence encoding a third antigen from a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), operably linked to an IRES or a SG promoter.
  10. 10. The RNA of claim 1, wherein the RNA is a monocistronic RNA.
  11. 11. The RNA of claim 1, wherein the RNA is a polycistronic RNA.
  12. 12. The RNA of claim 5, wherein the promoter is a subgenomic (SG) promoter.
  13. 13. The RNA of claim 12, wherein the SG promoter is a minimal SG promoter or an extended SG promoter.
  14. 14. The RNA of claim 13, 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.
  15. 15. The RNA of claim 13, wherein the minimal SG promoter is encoded by a sequence set forth in SEQ ID NO: 1.
  16. 16. The RNA of claim 13, wherein the extended SG promoter is encoded by a sequence set forth in SEQ ID NO: 5.
  17. 17. The RNA of claim 5, wherein the IRES is an IRES from encephalomyocarditis virus (EMCV), poliovirus (PV), human enterovirus, foot-and-mouth disease virus (FMDV), hepatitis C virus (HCV), classical swine fever virus (CSFV), murine leukemia virus (MLV), simian immunodeficiency virus (SIV), Eukaryotic translation initiation factor 4G (elF4G), Death-associated protein 5 (DAP5), cellular Myc (c-Myc), NF-KB- repressing factor (NRF), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF-2), platelet-derived growth factor B (PDGF B), Antennapedia, X-linked inhibitor of apoptosis (XIAP or Apaf-1), immunoglobulin heavy-chain binding protein BiP, or fibroblast growth factor la (FGF1A), GTX, or a combination thereof.
  18. 18. The RNA of claim 17, wherein the EMCV IRES is a wild-type IRES encoded by a sequence set forth in SEQ ID NO: 4.
  19. 19. The RNA of claim 1, wherein the antigens are expressed at substantially the same level.
  20. 20. The RNA of claim 1, wherein the antigen from a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a nucleocapsid (N) or spike (S) protein, optionally encoded by the sequence set forth in SEQ ID NO:21 or 22.

Description

COMBINATION RNA VACCINE RELATED APPLICATION DATA The present application claims priority from United States Patent Application No. 63/511,332 filed 30 June 2023 entitled “Combination RNA Vaccine”, 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 combination RNA vaccines and uses thereof. The present disclosure also relates to conventional mRNA vaccines and self -replicating RNA vaccines for the treatment of diseases or conditions including respiratory syncytial virus (RSV). BACKGROUND Respiratory viral infections are a significant threat to human health. 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. Recently, SAR-CoV-2 has been responsible for causing the ongoing worldwide pandemic of the severely infectious coronavirus disease 2019 (COVID- 19). Moreover, respiratory syncytial virus (RSV) is the single most common cause of respiratory hospitalization in infants, and reinfection remains common in later life. Whilst some vaccines are available for viral infections such as SARS-CoV-2 and RSV, such as mRNA vaccines developed to treat or prevent a SARS-CoV-2 infection, further improvements can be made to increase their efficacy and/or improve treatment strategies. Currently, egg-based manufacturing processes are the most common way that vaccines are produced. This process requires a significant amount of time to optimize virus growth in the eggs, as well as resources (i.e., eggs) to produce sufficient amounts of vaccine, particularly during a pandemic. Furthermore, given the long development time required, vaccine strain selection is conducted before the vaccine is made available, making it difficult to respond to changes in the virus. Vaccines have also been produced using cell-based manufacturing processes involving cultured mammalian cells (e.g. Madin-Darby Canine Kidney, or MDCK cells) in place of eggs, and viral-based platforms involving recombinant virus (e.g. baculo virus encoding an antigen of influenza) have also been utilised. There remains a need for the development of specific and efficient viral vaccines that can be produced more rapidly and with broader utility than current egg -based techniques, for the treatment or prevention of respiratory viral infections, such as RSV and SARS-CoV-2. Nucleic acid-based vaccines offer distinct advantages over the current egg-based manufacturing platform, although some challenges remain. For example, the inherently labile nature of mRNA results in most RNA-based vaccines having limited ability to provide antigen at a dose and duration required to produce a strong, durable immune response. Therefore, it will be apparent to the skilled person that there is a need in the art for compositions with broader utility and/or improved efficacy that are suitable for use as vaccines. 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, an antigen from influenza and an antigen from a respiratory syncytial virus (RSV) that is suitable as a vaccine for the treatment of a SARS-Cov-2 infection, coronavirus disease 2019 (COVID-19), influenza and/or RSV. 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, influenza and/or RSV, as well as complications thereof including acute respiratory distress syndrome (ARDS), in a subject. Accordingly, the present disclosure provides a polynucleotide comprising: (a) a nucleotide sequence encoding an antigen from a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); (b) a nucleotide sequence encoding a second antigen from influenza, and (c) a nucleotide sequence encoding a third antigen from a respiratory syncytial virus (RSV), wherein each nucleotide sequence is operably linked to a regulatory element. In an example, the polynucleotide comprises, in 5’ to 3’ order: (a) the nucleotide sequence encoding an antigen from a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); (b) the nucleotide sequence encoding an antigen from influenza, and (c) the nucleotide sequence encoding an antigen from a respiratory syncytial virus (RSV). In another example, the polynucleotide comprises, in 5’ to 3’ order: (a) the nucleotide sequence encoding an antigen from a respiratory syncytial virus (RSV); (b) the nucleotide sequence encoding an antigen from a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); and (c) the nucleotide sequence encoding an antigen from influenza. In another exa