Immunogenic compositions comprising sbi protein and uses thereof

Patent metadata

Field	Value
Publication number	US-2019282683-A1
Application number	US-201716463665-A
Country	US
Kind code	A1
Filing date	Nov 24, 2017
Priority date	Nov 25, 2016
Publication date	Sep 19, 2019
Grant date	—

Abstract

The invention relates to methods and compositions for use in stimulating an immune response against a target antigen. More specifically, it relates to use of domains III and IV of the Staphylococcal Sbi protein as an immunological adjuvant, for enhancing an immune response against a target antigen.

First claim

1 . A complement-activating moiety comprising Sbi-III-IV for use as an immunological adjuvant.

2 . A complement-activating moiety comprising Sbi-III-IV for use in a method of enhancing an immune response in a subject against a target antigen, wherein said complement-activating moiety is administered to a subject in conjunction with the target antigen.

3 . A complement-activating moiety for use according to claim 2 wherein the target antigen is a peptide antigen.

4 . A complement-activating moiety for use according to claim 2 wherein the target antigen comprises a carbohydrate, saccharide, polysaccharide, lipid or lipopolysaccharide.

5 . A complement-activating moiety for use according to any one of claims 2 to 4 wherein the target antigen is admixed with the complement-activating moiety.

6 . A complement-activating moiety for use according to claim 2 or claim 3 wherein the target antigen is covalently linked to the complement-activating moiety.

7 . A complement-activating moiety for use according to claim 6 wherein the target antigen forms a fusion protein with the complement-activating moiety.

8 . A complement-activating moiety for use according to claim 4 wherein the target antigen is covalently linked to a carrier peptide.

9 . A method of enhancing the immunogenicity of a target antigen, comprising contacting the target antigen in vitro or ex vivo with complement and a complement-activating moiety comprising Sbi-III-IV to yield an opsonised target antigen.

10 . A method according to claim 9 , further comprising the step of isolating the opsonised target antigen from other complement components and/or the complement activating moiety.

11 . A method according to claim 9 or claim 10 , further comprising the step of formulating the opsonised target antigen for administration to a subject.

12 . A method according to claim 9 or claim 10 further comprising administering the target antigen to a subject.

13 . A composition comprising an opsonised target antigen for use in a method of stimulating an immune response against the target antigen, wherein the target antigen has previously been contacted in vitro or ex vivo with complement and a complement-activating moiety comprising Sbi-III-IV.

14 . A complement-activating moiety for use according to any one of claims 2 to 8 , a method according to any one of claims 10 to 12 , or a composition for use according to claim 13 , wherein the target antigen is derived from an infectious organism.

15 . A complement-activating moiety for use, a method, or a composition for use, according to claim 14 , wherein the infectious organism is a bacterium, fungal cell, virus, protozoan, helminth or fluke.

16 . A complement-activating moiety for use, a method, or a composition for use, according to claim 15 , wherein the bacterium is:
Actinomyces (e.g. Actinomyces israelii ); Bacillus (e.g. Bacillus anthracis, Bacillus cereus ); Bacteroides (e.g. Bacteroides fragilis ); Bartonella (e.g. Bartonella henselae, Bartonella quintana ); Bordetella (e.g. Bordetella pertussis ); Borrelia (e.g. Borrelia burgdorferi, Borrelia garinii, Borrelia afzelii, Borrelia recurrentis ); Brucella (e.g. Brucella abortus, Brucella canis, Brucella melitensis, Brucella suis ); Campylobacter (e.g. Campylobacter jejuni ); Chlamydia and Chlamydophila (e.g. Chlamydia pneumoniae Chlamydia trachomatis Chlamydophila psittaci ); Clostridium (e.g. Clostridium botulinum, Clostridium difficile, Clostridium perfringens Clostridium tetani ); Corynebacterium (e.g. Corynebacterium diphtheriae ); Cryptococcus (e.g. Cryptococcus neoformans ); Ehrlichia (e.g. Ehrlichia canis, Ehrlichia chaffensis); Enterococcus (e.g. Enterococcus faecalis, Enterococcus faecium ); Escherichia (e.g. Escherichia coli ); Francisella (e.g. Francisella tularensis ); Haemophilus (e.g. Haemophilus influenzae ); Helicobacter (e.g. Helicobacter pylori ); Klebsiella (e.g. Klebsiella pneumoniae ); Legionella (e.g. Legionella pneumophila ); Leptospira (e.g. Leptospira interrogans, Leptospira santarosai, Leptospira weilii, Leptospira noguchii ); Listeria (e.g. Listeria monocytogenes ); Mycobacterium (e.g. Mycobacterium leprae, Mycobacterium tuberculosis, Mycobacterium ulcerans ); Mycoplasma (e.g. Mycoplasma pneumoniae ); Neisseria (e.g. Neisseria gonorrhoeae, Neisseria meningitidis ); Nocardia (e.g. Nocardia asteroides ); Pseudomonas (e.g. Pseudomonas aeruginosa ); Rickettsia (e.g. Rickettsia rickettsii ); Salmonella (e.g. Salmonella typhi, Salmonella typhimurium, Salmonella enterica ); Shigella (e.g. Shigella sonnei, Shigella dysenteriae; Shigella flexneri ); Staphylococcus (e.g. Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus ); Streptococcus (e.g. Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans ); Treponema (e.g. Treponema pallidum ); Ureaplasma (e.g. Ureaplasma urealyticum ); Vibrio (e.g. Vibrio cholerae ); or Yersinia (e.g. Yersinia pestis, Yersinia enterocolitica, Yersinia pseudotuberculosis ).

17 . A complement-activating moiety for use, a method, or a composition for use, according to claim 15 , wherein the fungal cell is:
Candida (e.g. Candida albicans, Candida glabrata, Candida rugosa, Candida parapsilosis, Candida tropicalis, Candida dubliniensis ); Aspergillus (e.g. Aspergillus fumigatus, Aspergillus flavus ); Cryptococcus (e.g. Cryptococcus neoformans ); Histoplasma (e.g. Histoplasma capsulatum ); Pneumocystis (e.g. Pneumocystis jirovecii, Pneumocystis carinii ); or Stachybotrys (e.g. Stachybotrys charatum )

18 . A complement-activating moiety for use, a method, or a composition for use, according to claim 15 , wherein the virus is of the type:
Adenoviridae (e.g. Adenovirus); Herpesviridae (e.g. Herpes simplex, type 1, Herpes simplex, type 2, Varicella-zoster virus, Epstein-Barr virus, Human cytomegalovirus, Human herpesvirus type 8); Papillomaviridae (e.g. Human papillomavirus); Polyomaviridae (e.g. BK virus, JC virus); Poxviridae (e.g. Smallpox); Hepadnaviridae (e.g. Hepatitis B virus); Parvoviridae (e.g. Parvovirus B19); Astroviridae (e.g. Human astrovirus); Caliciviridae (e.g. Norwalk virus); Picornaviridae (e.g. coxsackievirus, hepatitis A virus, poliovirus, rhinovirus); Coronaviridae (e.g. Severe acute respiratory syndrome virus); Flaviviridae (e.g. Hepatitis C virus, yellow fever virus, dengue virus, West Nile virus, TBE virus); Togaviridae (e.g. Rubella virus); Hepeviridae (e.g. Hepatitis E virus); Retroviridae (e.g. Human immunodeficiency virus (HIV), Human T-cell leukaemia virus (HTLV) types I, II, III and IV); Orthomyxoviridae (e.g. Influenza virus); Arenaviridae (e.g. Lassa virus); Bunyaviridae (e.g. Crimean-Congo hemorrhagic fever virus, Hantaan virus); Filoviridae (e.g. Ebola virus, Marburg virus); Paramyxoviridae (e.g. Measles virus, Mumps virus, Parainfluenza virus, Respiratory syncytial virus); Rhabdoviridae (e.g. Rabies virus); Hepatitis D virus; Reoviridae (e.g. Rotavirus, Orbivirus, Coltivirus, Banna virus).

19 . A complement-activating moiety for use, a method, or a composition for use, according to claim 15 , wherein the protozoan is:
Plasmodium spp. (responsible for malaria, e.g. Plasmodium falciparum, Plasmodium berghei, Plasmodium yoelii, Plasmodium

Assignees

• Univ Bath

Inventors

• Van Den Elsen Jean
• Watts Andrew Graham
• Marchbank Kevin James

Classifications

• A61K2039/55566

  Emulsions, e.g. Freund's adjuvant, MF59 · CPC title

• A61K2039/55516

  Proteins; Peptides · CPC title

• A61K2039/6068

  Other bacterial proteins, e.g. OMP · CPC title

• A61K39/04

  Mycobacterium, e.g. Mycobacterium tuberculosis · CPC title

• A61K39/385

  Haptens or antigens, bound to carriers · CPC title