Chimeric filovirus vaccines

Patent metadata

Field	Value
Publication number	US-12545709-B2
Application number	US-202017642791-A
Country	US
Kind code	B2
Filing date	Sep 4, 2020
Priority date	Sep 13, 2019
Publication date	Feb 10, 2026
Grant date	Feb 10, 2026

Abstract

The present invention relates to polynucleotides comprising a sequence of a live, infectious, attenuated Flavivirus wherein a nucleotide sequence encoding at least a part of a Filovirus glycoprotein is located at the intergenic region between the E and NS1 gene of said Flavivirus, such that a chimeric virus is expressed, characterised in that the encoded sequence C terminally of the E protein of said Flavivirus and N terminally of the signal peptide of the NS1 protein of said Flavivirus comprises in the following order: a further signal peptide of a Flavivirus NS1 protein, a filovirus glycoprotein wherein the N terminal signal peptide is absent, a TM domain of a flaviviral E protein.

First claim

The invention claimed is:

1 . A polynucleotide comprising a sequence of a live, infectious, attenuated Flavivirus, the polynucleotide comprising:
a nucleotide sequence that encodes at least a part of a Filovirus glycoprotein lacking an N terminal signal peptide,
wherein:
the nucleotide sequence is located at an intergenic region between an E gene of the Flavivirus and an NS1 gene of the Flavivirus, the E gene encoding an E protein, the NS1 gene encoding an NS1 protein, the NS1 protein comprising a signal peptide, such that a chimeric virus is expressed; and
the nucleotide sequence is translatable such that the nucleotide sequence encodes a chimeric viral peptide, the chimeric viral peptide comprising:
(a) a further signal peptide, positioned C terminally of the E protein, the further signal peptide having the same sequence as the signal peptide of the NS1 protein,
(b) the Filovirus glycoprotein, positioned C terminally of the further signal peptide, and
(c) a TM domain of a further Flaviviral E protein, positioned C terminally of the Filovirus glycoprotein; and

the chimeric viral peptide is positioned N terminally of the NS1 protein of the Flavivirus.

2 . The polynucleotide according to claim 1 , wherein the Flavivirus is Yellow Fever virus.

3 . The polynucleotide according to claim 1 , wherein the Filovirus is a mononegavirus.

4 . The polynucleotide according to claim 3 , wherein the Filovirus is an Ebola virus.

5 . The polynucleotide according to claim 1 , wherein the further signal peptide comprises the sequence set forth in SEQ ID NO:9.

6 . The polynucleotide according to claim 1 , wherein the TM domain of the further Flaviviral E protein is a TM2 domain from West Nile virus.

7 . The polynucleotide according to claim 1 , wherein the Filovirus glycoprotein lacks the N terminal signal sequence set forth in SEQ ID NO:6.

8 . The polynucleotide according to claim 1 , wherein the Filovirus glycoprotein lacks a mucin like domain set forth in SEQ ID NO:7.

9 . The polynucleotide according to claim 1 , further comprising a junction sequence, wherein the junction sequence is selected from the group consisting of:
the junction sequence set forth in SEQ ID NO:11, positioned between the further signal peptide and the Filovirus glycoprotein; the junction sequence set forth in SEQ ID NO:12, positioned between the Filovirus glycoprotein and the TM domain; and the junction sequence set forth in SEQ ID NO:13, positioned between the TM domain and the NS1 protein.

10 . The polynucleotide according to claim 1 , wherein the nucleotide sequence comprises:
a nucleotide sequence that is 95% identical to the nucleotide sequence set forth in SEQ ID NO:1; or a nucleotide sequence that is 95% identical to the nucleotide sequence set forth in SEQ ID NO:3.

11 . The polynucleotide according to claim 1 , wherein the nucleotide sequence further comprises the nucleotide sequences encoding for the peptide sequences set forth in SEQ ID NO:11, SEQ ID NO:12 and SEQ ID NO:13.

12 . A pharmaceutical composition comprising the polynucleotide sequence according to claim 1 and at least one pharmaceutically acceptable carrier, diluent, or excipient.

13 . A method of vaccinating an individual against a Filovirus infection, the method comprising administering to the individual a polynucleotide sequence according to claim 1 .

14 . A chimeric live, infectious, attenuated Flavivirus comprising:
an E protein; an NS1 protein comprising a signal peptide; and a chimeric protein comprising:
at least a part of a Filovirus glycoprotein lacking a functional signal peptide, wherein the Filovirus glycoprotein is inserted between the E protein and the NS1 protein;
a further signal peptide, positioned C terminally of the E protein, wherein the further signal peptide has the same sequence as the signal peptide of the NS1 protein, and wherein the Filovirus glycoprotein is positioned C terminally of the further signal peptide; and
a TM domain of a further Flaviviral E protein, positioned C terminally of the Filovirus glycoprotein,
wherein the chimeric peptide is positioned N terminally of the NS1 protein.

15 . The chimeric live, infectious, attenuated Flavivirus according to claim 14 , wherein said Filovirus is Ebolavirus.

16 . The chimeric live, infectious, attenuated Flavivirus according to claim 14 , wherein the Flavivirus is Yellow Fever virus.

17 . The chimeric live, infectious, attenuated Flavivirus according to claim 14 , wherein the Filovirus glycoprotein lacks the N terminal signal sequence set forth in SEQ ID NO:6.

18 . A pharmaceutical composition comprising the chimeric live, infectious, attenuated Flavivirus according to claim 14 and at least one pharmaceutically acceptable carrier, diluent, or excipient.

19 . A method of vaccinating an individual against a Filovirus infection, the method comprising administering to the individual the chimeric live, infectious, attenuated Flavivirus according to claim 14 .

20 . A chimeric live, infectious, attenuated Flavivirus according to claim 14 , wherein the flavivirus comprises an amino acid sequence that is 95% identical to the amino acid sequence set forth in SEQ ID NO:2 or an amino acid sequence that is 95% identical to the amino acid sequence set forth in SEQ ID NO:4.

Assignees

• Univ Leuven Kath

Inventors

• Dallmeier Kai
• Sanchez Felipe Lorena
• Lemmens Viktor
• Neyts Johan

Classifications

• C12N2770/24171

  Demonstrated in vivo effect · CPC title

• C12N2770/24134

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title

• C12N2770/24122

  New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes · CPC title

• C07K2319/02

  containing a signal sequence · CPC title

• A61K2039/5254

  avirulent or attenuated · CPC title