Immunogenic composition against Campylobacter jejuni
Inventors
Guerry, Patricia • Monteiro, Mario Artur
Assignees
Publication Number
US-9999591-B2
Publication Date
2018-06-19
Expiration Date
2026-09-20
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Abstract
The inventive subject matter relates to an immunogenic composition against Campylobacter jejuni comprising isolated capsule polysaccharide from selected pathogenic Campylobacter jejuni strains. The inventive subject matter also relates to methods of using the polysaccharide compositions in inducing and anti-C. jejuni immune response.
Core Innovation
The invention relates to an immunogenic composition comprising isolated capsule polysaccharides from selected pathogenic Campylobacter jejuni strains to form polysaccharide polymers. The composition is devoid of lipooligosaccharide (LOS) structures and other components associated with Guillain Barré Syndrome (GBS) and autoimmune disorders. These polysaccharide antigens are derived from specific C. jejuni strains, including HS1, HS1/HS44, HS44, HS2, HS3, HS4, HS5, HS13, HS4/13/64, and HS50. The composition can contain one or more polysaccharide antigens and can be conjugated to a protein carrier such as CRM197.
The invention addresses the lack of licensed vaccines against C. jejuni, a major cause of diarrheal disease worldwide that is associated with severe complications such as Guillain-Barré Syndrome due to molecular mimicry between LOS cores and human gangliosides. Whole cell vaccines or vaccines containing LOS components pose a risk of inducing autoimmune responses. Therefore, the problem being solved is the development of an immunogenic composition that induces protection against C. jejuni infections without including LOS, thereby reducing the risk of autoimmune reactions.
Claims Coverage
The patent includes multiple independent claims covering immunogenic compositions and methods of inducing immune responses against Campylobacter jejuni, focusing on isolated capsule polysaccharide antigens from specific strains and their formulations and administration.
Composition comprising isolated capsule polysaccharide antigens from specific C. jejuni strains conjugated to a protein carrier
An immunogenic composition against Campylobacter jejuni comprising one or more polysaccharide antigens, each being an isolated capsule polysaccharide from strains HS4, HS4/13/64, HS5, and HS50, formed into repeating polysaccharide polymers with 1 to 100 repeats, devoid of lipooligosaccharide structures associated with Guillain Barré Syndrome, where the polysaccharide polymers are conjugated to a protein carrier.
Specific polysaccharide structures derived from C. jejuni strains
The polysaccharide antigens comprise specific structural motifs such as →3)-L-β-D-ido-Hep-(1→4)-β-D-GlcNAc-(1→ with non-stoichiometric methyl phosphoramidate (MeOPN) substitution, and variations thereof depending on the originating C. jejuni strain.
Protein carrier selection and adjuvant inclusion
The protein carrier used for conjugation can be CRM197, and the immunogenic composition may also include adjuvants such as LTR192G, aluminum hydroxide, RC529, QS21, E294, oligodeoxynucleotides (ODN), CpG-containing oligodeoxynucleotides, or aluminum phosphate.
Method for inducing an immune response against C. jejuni strains
A method of inducing an anti-Campylobacter jejuni immune response in mammals by administering the described immunogenic compositions in one or more doses within a dosage range of 0.1 μg to 10 mg per dose, optionally with adjuvants and by various administration routes including oral, nasal, subcutaneous, intradermal, transdermal, transcutaneous, intramuscular, or rectal.
The claims cover immunogenic compositions composed of isolated capsule polysaccharide antigens from specified Campylobacter jejuni strains conjugated to protein carriers and methods for inducing immune responses in mammals through administration of these compositions with or without adjuvants by various routes.
Stated Advantages
Induction of a protective immune response against C. jejuni without the inclusion of lipooligosaccharide structures, thereby minimizing the risk of autoimmune responses such as Guillain Barré Syndrome.
Cross-reactivity of antibodies resulting from immunization with certain polysaccharide antigens, for example, immunity induced by HS1 antigens also providing protection against HS44 strains.
Ability to conjugate isolated capsule polysaccharides to protein carriers (e.g., CRM197) to enhance immunogenicity.
Documented Applications
Use of isolated Campylobacter jejuni capsule polysaccharides in immunogenic compositions for vaccination against diarrheal disease caused by C. jejuni strains including HS1, HS44, HS5, HS4, HS13, HS50, and their complexes.
Methods of inducing an immune response in mammals by administration of polysaccharide-based immunogenic compositions derived from specified C. jejuni capsule polysaccharides, with or without adjuvants, through multiple routes.
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