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EP-4735025-A2 - RECOMBINANT VIRUS-LIKE PARTICLES

EP4735025A2EP 4735025 A2EP4735025 A2EP 4735025A2EP-4735025-A2

Abstract

The present disclosure relates to a recombinant virus-like particle (VLP) comprising an antigen for use as a vaccine. In an aspect, the present disclosure relates to a recombinant VLP comprising a capsid fusion protein for use as a vaccine.

Inventors

  • Cai, Yongfei

Assignees

  • Seqirus Inc.

Dates

Publication Date
20260506
Application Date
20240628

Claims (20)

  1. 1. A recombinant virus-like particle (VLP) comprising a capsid fusion protein and a lipid bilayer, the capsid fusion protein comprising: (a) a capsid protein from a non-enveloped virus; (b) a transmembrane (TM) protein domain; and (c) an antigen protein, wherein the capsid protein is encapsulated within the lipid bilayer.
  2. 2. The recombinant VLP of claim 1, wherein the capsid protein from a non-enveloped virus is from an alfalfa mosaic virus (AMV), bacteriophage MS2 or bacteriophage AP205.
  3. 3. The recombinant VLP of claim 2, wherein the capsid protein is a dimer.
  4. 4. The recombinant VLP of claim 1, wherein the capsid protein is fused to the TM protein domain by a peptide linker.
  5. 5. The recombinant VLP of claim 1, wherein the TM protein domain and the antigen protein are from a virus.
  6. 6. The recombinant VLP of claim 5, wherein the TM protein domain and the antigen protein are from the same virus.
  7. 7. The recombinant VLP of claim 5, wherein the TM protein domain and the antigen protein are from different viruses.
  8. 8. The recombinant VLP of claim 1, wherein the antigen protein and the TM protein domain are from a SARS-CoV-2.
  9. 9. The recombinant VLP of claim 1, wherein the antigen protein and the TM protein domain are from a Spike (S) protein of a SARS-CoV-2.
  10. 10. The recombinant VLP of claim 9, wherein the S protein lacks the furin cleavage site at the the S1/S2 boundary and/or the S2’ site.
  11. 11. The recombinant VLP of claim 1, wherein the antigen protein and the TM protein domain are from influenza.
  12. 12. The recombinant VLP of claim 1, wherein the antigen protein is a haemagluttinin (HA) protein or neuroaminidase (NA) protein from influenza.
  13. 13. The recombinant VLP of claim 1 , wherein the antigen protein and the TM protein are from a respiratory syncytial virus (RSV).
  14. 14. The recombinant VLP of claim 1, wherein the antigen protein is a F protein from RSV.
  15. 15. The recombinant VLP of claim 1, wherein the VLP does not include any viral RNA.
  16. 16. The recombinant VLP of claim 1, wherein the VLP has a diameter of between about 70nm and 160nm.
  17. 17. The recombinant VLP of claim 16, wherein the VLP has a diameter of about 80nm.
  18. 18. The recombinant VLP of claim 1, wherein the VLP is formulated in a lipid nanoparticle (LNP).
  19. 19. An isolated, recombinant or synthetic nucleotide sequence encoding the VLP of claim 1.
  20. 20. An expression vector comprising the nucleotide sequence of claim 19.

Description

RECOMBINANT VIRUS-LIKE PARTICLES RELATED APPLICATION DATA The present application claims priority from United States Patent Application No. 63/510,970 filed 29 June 2023 entitled “Recombinant virus-like particles”, 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 a recombinant virus-like particle (VLP) comprising an antigen for use as a vaccine. In an aspect, the present disclosure relates to a recombinant VLP comprising a capsid fusion protein for use as a vaccine. 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 on-going 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 influenza, SARS-CoV-2 and RSV, 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. baculovirus 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 influenza, 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 recombinant virus-like particles (VLPs) comprising a capsid fusion protein and a lipid bilayer that are suitable for the treatment of a disease, condition or infection, such as a SARS-CoV-2 infection, influenza or coronavirus disease 2019 (COVID-19). The findings by the inventors therefore provide basis for methods of treating or preventing or delaying progression of a disease, condition or infection, such as a SARS-CoV-2 infection or COVID-19, as well as complications thereof including pneumonia and acute respiratory distress syndrome (ARDS)) in a subject. The lipid bilayer present in the VLPs described in the present disclosure provides for a technical advantage by preventing an immune response in the subject to the capsid protein that forms part of the capsid fusion protein. Further, the VLP constructs provided by the present disclosure are capable of assembling into VLPs and providing immunogenicity in the form of a vaccine. Accordingly, the present disclosure provides a recombinant virus-like particle (VLP) comprising a capsid fusion protein and a lipid bilayer, the capsid fusion protein comprising: (a) a capsid protein from a non-enveloped virus; (b) a transmembrane (TM) protein domain; and (c) an antigen protein, wherein the capsid protein is encapsulated within the lipid bilayer. The present disclosure also provides a virus-like particle (VLP) comprising a capsid fusion protein and a lipid bilayer, the capsid fusion protein comprising: (a) a capsid protein from a non-enveloped virus; and (b) an antigen protein, wherein the capsid protein is encapsulated within the lipid bilayer. In one example, the capsid protein from a non-enveloped virus is from an alfalfa mosaic virus (AMV), bacteriophage MS2 or bacteriophage AP205. In one example, the capsid protein is from AMV. In some examples,