Immunogenic composition against Campylobacter jejuni
Inventors
Guerry, Patricia • Monteiro, Mario Artur
Assignees
Publication Number
US-10765627-B2
Publication Date
2020-09-08
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 an anti-C. jejuni immune response.
Core Innovation
The invention relates to an immunogenic composition against Campylobacter jejuni comprising isolated capsule polysaccharides derived from selected pathogenic C. jejuni strains. The composition includes one or more polysaccharide antigens, each comprising isolated polysaccharides or polysaccharide polymers obtained from strains such as HS1, HS1/HS44, HS44, HS2, HS3, HS4, HS5, HS13, HS4/13/64, and HS50. These polysaccharides are isolated away from lipooligosaccharide (LOS) structures associated with Guillain-Barré Syndrome (GBS) and other autoimmune disorders, ensuring the immunogenic composition is devoid of components that could cause autoimmunity.
The problem addressed arises from the heavy disease burden caused by C. jejuni, which leads to diarrheal illness worldwide and is a significant cause of pediatric disease in developing countries. A major challenge for vaccine development is the molecular mimicry between C. jejuni LOS cores and human gangliosides, which is associated with GBS, a serious post-infectious neuropathy. Existing vaccine attempts are limited because inclusion of LOS components induces autoimmune responses. Moreover, despite over 47 Penner serotypes identified, most disease is caused by a limited number of serotypes, necessitating targeted vaccine development using selected capsule polysaccharides.
The invention further presents methods of inducing an immune response against C. jejuni by administering compositions comprising these isolated capsule polysaccharides or polymers. These polysaccharides can be conjugated to carrier proteins such as CRM197 to enhance immunogenicity. Detailed chemical structures and compositions of the polysaccharides from multiple strains are provided, including the HS1/HS44 complex teichoic-acid like polymers, HS5 polysaccharide variants, and polysaccharides from HS4 complex strains. Animal immunization studies demonstrate the induction of significant anti-C. jejuni IgG responses without inclusion of LOS components, indicating a safe and effective approach to vaccine design.
Claims Coverage
The claims encompass polysaccharide antigens and immunization methods against Campylobacter jejuni strains, with inventive features focused on polysaccharide structure, composition, and conjugation.
Polysaccharide antigen comprising isolated capsule polysaccharides from selected C. jejuni strains
A polysaccharide antigen for inducing immune response composed of isolated C. jejuni capsule polysaccharides from strains HS4, HS5, HS4/13/64, and HS50, linked to form repeating polysaccharide polymers with 2 or more repeats, devoid of LOS structures associated with Guillain-Barré Syndrome.
Defined polysaccharide structures of HS4, HS5, HS4/13/64, and HS50 strains
Detailed polysaccharide structures with non-stoichiometric O-methyl phosphoramidate (MeOPN) substitutions are specified for the strains, including →3)-L-β-D-ido-Hep-(1→4)-β-D-GlcNAc-(1→ for HS4 and variants for HS5 and HS50, with the number of repeats 'n' from 1 to 100.
Conjugation of polysaccharide polymers to protein carriers
Polysaccharide polymers are conjugated to protein carriers, specifically CRM197, to enhance immunogenicity.
Method of immunizing against C. jejuni strains HS4, HS13, HS4/13/64, and HS50 using polysaccharide antigens
Administering one or more antigens comprising the polysaccharide antigens as described to immunize subjects against these C. jejuni strains, optionally including a protein carrier and adjuvants like LTR192G, aluminum hydroxide, and CpG-containing oligodeoxynucleotides.
The claims cover isolated capsule polysaccharide antigens from specific C. jejuni strains, their conjugation to protein carriers such as CRM197, and methods of immunization using these antigen compositions along with adjuvants to induce protective immune responses while excluding harmful LOS components.
Stated Advantages
The immunogenic compositions are free of lipooligosaccharide structures associated with Guillain-Barré Syndrome, reducing the risk of autoimmune responses.
The compositions induce specific immune responses against prevalent pathogenic C. jejuni serotypes responsible for most diarrheal disease.
Conjugation of polysaccharides to carrier proteins enhances immunogenicity and antibody response in experimental animals.
Use of selected capsule polysaccharides overcomes limitations of prior vaccine approaches by targeting capsule antigens instead of LOS.
Documented Applications
Inducing an immune response against Campylobacter jejuni strains prevalent in human disease via administration of isolated capsule polysaccharide antigens.
Use of polysaccharide-protein conjugate vaccines comprising CRM197 for immunization protocols in mammals.
Vaccine development aiming to protect against diarrhea caused by C. jejuni without inducing Guillain-Barré Syndrome.
Application in immunizing subjects against multiple related C. jejuni serotypes grouped in the HS1, HS4, and HS5 complexes.
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