Boosting sars-cov-2 immunity with a lentiviral-based nasal vaccine

Patent metadata

Field	Value
Publication number	US-2025090655-A1
Application number	US-202318726286-A
Country	US
Kind code	A1
Filing date	Jan 17, 2023
Priority date	Jan 17, 2022
Publication date	Mar 20, 2025
Grant date	—

Abstract

The invention relates to the field of immunity against coronaviruses. In this respect, the invention provides a lentiviral-based immunogenic agent that is suitable for use in boost or target immunization treatment in a subject, in particular a human subject, who had previously developed an immunity against Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) based on: (i) vaccination with the first generation of vaccines against SARS-CoV-2 infection or disease such as a protein, an mRNA, an adenovirus, an inactivated virus or a protein subunit vaccine composition against SARS-CoV-2 infection or disease, in particular a protein- or an mRNA-based vaccine, or (ii) SARS-CoV-2-induced or correlated disease. The invention accordingly concerns a lentiviral-based immunogenic agent that in particular may help overcome the deficiencies of available vaccines against SARS-CoV-2, especially may be efficient in overcoming the waning immune response or insufficient cellular memory response observed after immunization with available first generation of vaccines such as a protein, an mRNA, an adenovirus, an inactivated virus or a protein subunit vaccine, in particular protein or mRNA vaccine, by triggering a mucosal humoral and cellular immune response against coronaviruses, including a long-lasting immune response.

First claim

1 - 18 . (canceled)

19 . A method for heterologous boosting in a vaccine regimen comprising administrating a pseudotyped lentiviral vector particle encoding a Spike (S) protein of a Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) to the upper respiratory tract of a human subject who has received a prime immunization with a SARS-CoV-2 vaccine composition selected from the group consisting of a protein, an mRNA, an adenovirus, an inactivated virus and a protein subunit vaccine composition.

20 . The method of claim 19 , wherein the administration is performed as intranasal mucosal boost immunization.

21 . The method of claim 19 , wherein the S protein of SARS-CoV-2 is (i) an S protein from a SARS-CoV-2 virus selected from the group consisting of SARS-CoV-2 Ancestral strain, D614G strain, Alpha strain, Beta strain, Gamma strain, Delta strain and Omicron strain or (ii) an S protein from a variant of said Ancestral, D614G, Alpha, Beta, Gamma, Delta or Omicron strains, wherein such variant encodes a Spike protein with an amino acid sequence at least 90% identity to SEQ ID NO: 1.

22 . The method of claim 19 , wherein S protein of SARS-CoV-2 is (a) a stabilized form of the S protein characterized by substitution of two consecutive amino acid residues for Proline residues in the S2 domain of the S protein at positions provided as residues 986 and 987 by reference to SEQ ID NO: 1 in the amino acid sequence of the Spike protein or (b) is a prefusion form of the S protein by deletion of the furin site located from residue 675 to residue 685 by reference to SEQ ID NO: 1 in the amino acid sequence of the S protein or (c) is a stabilized prefusion form of the S protein by deletion of the furin site and substitution of two consecutive amino acid residues for Proline residues in the S2 domain at positions 986 and 987 by reference to SEQ ID NO: 1.

23 . The method of claim 19 , wherein the amino acid sequence of the S protein of SARS-CoV-2 is SEQ ID NO: 1 or an amino acid sequence having at least 90% identity to SEQ ID NO: 1, and wherein the S protein of SARS-CoV-2 comprises at least five amino acid mutations including (i) a mutation of the lysine residue to the asparagine residue at position 417 of the amino acid sequence of SEQ ID NO: 1 (K417N), (ii) a mutation of the glutamic acid residue to the lysine residue at position 484 of the amino acid sequence of SEQ ID NO: 1 (E484K) or a mutation of the glutamic acid residue to the alanine residue at position 484 of the amino acid sequence of SEQ ID NO: 1 (E484A), (iii) a mutation of the asparagine residue to the tyrosine residue at position 501 of the amino acid sequence of SEQ ID NO: 1 (N501Y), (iv) a mutation of the lysine residue to the proline residue at position 986 of the amino acid sequence of SEQ ID NO: 1 (K986P) and (v) a mutation of the valine residue to the proline residue at position 987 of the amino acid sequence of SEQ ID NO: 1 (V987P).

24 . The method of claim 19 , wherein the subject receiving administration of the composition is a subject that has received a an intramuscular, intradermal or sub-cutaneous prime administration of a protein- or an mRNA-based vaccine composition against SARS-CoV-2 infection or disease.

25 . The method of claim 23 , wherein the S protein of SARS-CoV-2 further comprises amino acid mutations selected from the group consisting of (vi) a mutation of the glycine residue to the serine residue at position 446 of the amino acid sequence of SEQ ID NO: 1 (G446S), (vii) a mutation of the threonine residue to the lysine residue at position 478 of the amino acid sequence of SEQ ID NO: 1 (T478K), (viii) a mutation of the glutamine residue to the arginine residue at position 493 of the amino acid sequence of SEQ ID NO: 1 (Q493R) and (ix) a mutation of the glutamine residue to the arginine residue at position 498 of the amino acid sequence of SEQ ID NO: 1 (Q498R).

26 . The method of claim 19 , wherein the S protein of SARS-CoV-2 has the amino acid sequence of SEQ ID NO: 10 or SEQ ID NO: 18.

27 . The method of claim 19 , wherein the pseudotyped lentiviral vector particle is pseudotyped with a Vesicular Stomatitis Virus glycoprotein G (VSV-G) protein.

28 . The method of claim 19 , wherein the pseudotyped lentiviral vector particle elicits a CD8 + T-cell response against SARS-CoV-2.

29 . The method of claim 28 , wherein the pseudotyped lentiviral vector particle elicits lung-resident memory CD8 + T cells (Trm) and/or effector CD8 + T cells (Tc1) specific to Spike and produce Interferon-gamma (IFN-γ)/Tumor Necrosis Factor (TNF)/Interleukin-2 (IL-2).

30 . The method of claim 19 , wherein the pseudotyped lentiviral vector particle is non-integrative, non-cytopathic and non-replicative.

31 . The method of claim 19 , wherein the subject has a waning immunity from week 12 after the first injection of the initial vaccination with a vaccine composition against SARS-CoV-2 infection or disease.

32 . The method of claim 19 , wherein the pseudotyped lentiviral vector particle is formulated as a liquid composition or a dry powder for an administration as intranasal aerosols, intranasal drops or intranasal insufflations.

33 . The method of claim 19 , wherein the administration regimen comprises administration of one or more dosage form(s) of the pseudotyped lentiviral vector particle, wherein the dose of each dosage form is from 10 7 to 10 9 Transduction Unit (TU).

34 . The method of claim 19 , wherein the prime immunization is with protein SARS-CoV-2 vaccine composition.

35 . The method of claim 19 , wherein the prime immunization is with an mRNA SARS-CoV-2 vaccine composition.

36 . An immunogenic composition comprising a pseudotyped lentiviral vector particle encoding an S protein of a SARS-CoV-2 and a pharmaceutically acceptable carrier, wherein the S protein of SARS-CoV-2 comprises at least nine amino acid mutations including (i) a mutation of the lysine residue to the asparagine residue at position 417 of the amino acid sequence of SEQ ID NO: 1 (K417N), (ii) a mutation of the glutamic acid residue to the alanine residue at position 484 of the amino acid sequence of SEQ ID NO: 1 (E484A), (iii) a mutation of the asparagine residue to the tyrosine residue at position 501 of the amino acid sequence of SEQ ID NO: 1 (N501Y), (iv) a mutation of the lysine residue to the proline residue at position 986 of the amino acid sequence of SEQ ID NO: 1 (K986P), (v) a mutation of the valine residue to the proline residue at position 987 of the amino acid sequence of SEQ ID NO: 1 (V987P), (vi) a mutation of the glycine residue to the serine residue at position 446 of the amino acid sequence of SEQ ID NO: 1 (G446S), (vii) a mutation of the threonine residue to the lysine residue at position 478 of the amino acid sequence of SEQ ID NO: 1 (T478K), (viii) a mutation of the glutamine residue to the arginine residue at position 493 of the amino acid sequence of SEQ ID NO: 1 (Q493R) and (ix) a mutation of the glutamine residue to the arginine residue at position 498 of the amino acid sequence of SEQ ID NO: 1 (Q498R).

37 . The immunogenic composition according to claim 36 , wherein the S protein of SARS-CoV-2 has the amino acid sequence of SEQ ID NO: 18.

38 . The immunogenic composition according to claim 37 , which is formulated for intranasal administration.

Assignees

• Pasteur Institut
• Theravectys

Inventors

• Charneau Pierre
• Majlessi Laleh
• Bourgine Maryline
• Vesin Benjamin
• Lopez Jodie
• Fert Ingrid

Classifications

• A61K2039/543

  intranasal · CPC title

• A61K2039/5256

  expressing foreign proteins · CPC title

• A61P37/04

  Immunostimulants · CPC title

• C12N2740/15023

  Virus like particles [VLP] · CPC title

• C12N2740/15043

  viral genome or elements thereof as genetic vector · CPC title