Filovirus therapy
The present invention provides antibodies, for use in the treatment, suppression prevention of Filovirus disease, particularly Ebola virus disease. Also provided immunogens for use in eliciting such antibodies.
1. A composition comprising ovine polyclonal antibodies in a form suitable for administration in treating, suppressing or preventing Ebola virus disease in a patient, wherein said antibodies bind to Ebola virus glycoprotein, wherein said ovine polyclonal antibodies are raised against a recombinant Ebola virus glycoprotein, and wherein said recombinant Ebola virus glycoprotein lacks the endogenous transmembrane domain.
2. The composition according to claim 1 , wherein said composition comprises one or more additional therapeutics.
3. The composition according to claim 1 , wherein said one or more additional therapeutics targets a different component of said Ebola virus from said antibody.
4. The composition according to claim 1 , wherein said recombinant Ebola virus glycoprotein lacks the endogenous transmembrane domain and the endogenous membrane-proximal external region.
5. The composition according to claim 1 , wherein the recombinant Ebola virus glycoprotein also lacks the endogenous signal peptide.
6. The composition according to claim 1 , wherein the recombinant Ebola virus glycoprotein comprises or consists of an amino acid sequence having 70% or more identity to SEQ ID NO: 2 and comprises an epitope of SEQ ID NO: 2.
7. The composition according to claim 1 , wherein the recombinant Ebola virus glycoprotein comprises a fragment of at least 7 consecutive amino acids of SEQ ID NO: 2, and comprises an epitope of SEQ ID NO: 2.
8. The composition according to claim 1 , wherein the ovine polyclonal antibodies are produced by a method comprising:
(i) administering to a sheep a recombinant Ebola virus glycoprotein, wherein said recombinant Ebola virus glycoprotein lacks the endogenous transmembrane domain,
(ii) allowing sufficient time for the generation of antibodies in the sheep, and
(iii) obtaining the antibodies from the sheep.
9. A method of treating, suppressing or preventing Ebola virus disease in a patient, said method comprising administering to a patient an antibody composition comprising ovine polyclonal antibodies, wherein said polyclonal antibodies bind to Ebola virus glycoprotein, and wherein said polyclonal antibodies do not substantially bind to the endogenous transmembrane domain of Ebola virus glycoprotein, and wherein said ovine polyclonal antibodies are raised against recombinant Ebola virus glycoprotein, wherein said recombinant Ebola virus glycoprotein lacks the endogenous transmembrane domain.
10. The method according to claim 9 , wherein said treating, suppressing or preventing comprises intravenous administration of said composition to said patient, oral administration of said composition to said patient, intraperitoneal administration of said composition to said patient, or intramuscular administration of said composition to said patient.
11. The method according to claim 9 , wherein said patient is a mammal.
12. The method according to claim 9 , wherein said mammal is a human.
13. The method according to claim 9 , wherein said treating or suppressing comprises administering the composition to the patient within 5 days of infection with Ebola virus, within 2 days of infection with Ebola virus, within 1 day of infection with Ebola virus, within 12 hours of infection with Ebola virus, or more than 5 days after infection with Ebola virus.
14. The method according to claim 9 , wherein said preventing comprises administering the composition to the patient prior to infection with Ebola virus.
15. The method according to claim 9 , wherein said treating, suppressing or preventing comprises administration of one or more additional therapeutics.
16. The method according to claim 9 , wherein said one or more additional therapeutics targets a different component of said Ebola virus from said antibody.
17. The method according to claim 9 , wherein said ovine polyclonal antibodies are raised against recombinant Ebola virus glycoprotein, wherein said recombinant Ebola virus glycoprotein lacks the endogenous transmembrane domain and the endogenous membrane-proximal external region.
18. The method according to claim 17 , wherein the recombinant Ebola virus glycoprotein comprises or consists of an amino acid sequence having 70% or more identity to SEQ ID NO: 2 and comprises an epitope of SEQ ID NO: 2, or comprises a fragment of at least 7 consecutive amino acids of SEQ ID NO: 2, and comprises an epitope of SEQ ID NO: 2.
19. The method according to claim 17 , wherein the ovine polyclonal antibodies are produced by a method comprising:
(i) administering to a sheep the recombinant Ebola virus glycoprotein, wherein said recombinant Ebola virus glycoprotein lacks the endogenous transmembrane domain,
(ii) allowing sufficient time for the generation of antibodies in the sheep, and
(iii) obtaining the antibodies from the sheep.