Immunogenic composition against Campylobacter jejuni
Inventors
Guerry, Patricia • Monteiro, Mario Artur
Assignees
Publication Number
US-10363213-B2
Publication Date
2019-07-30
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 comprising isolated capsule polysaccharides from selected pathogenic Campylobacter jejuni strains. These polysaccharide antigens are linked to form polysaccharide polymers and are isolated specifically away from lipooligosaccharide (LOS) structures and other components associated with Guillain-Barré Syndrome or autoimmune disorders. The invention also encompasses methods for inducing an immune response against C. jejuni by administering these polysaccharide compositions.
Campylobacter jejuni is a significant cause of diarrheal disease worldwide, with symptoms including diarrhea, abdominal pain, and fever. A major complication associated with C. jejuni infection is Guillain-Barré Syndrome (GBS), which is linked to molecular mimicry between LOS cores of C. jejuni and human gangliosides, leading to an autoimmune response. There is no licensed vaccine against C. jejuni despite its clinical importance. The existing problem lies in inducing protective immunity without triggering autoimmune complications potentially caused by LOS-related molecular mimicry.
The inventive solution isolates capsule polysaccharides from selected C. jejuni strains, such as HS1, HS44, HS5, HS13, HS4/13/64, and HS50, which are responsible for most diarrheal diseases and are not associated with LOS or autoimmune responses. These polysaccharides can be used individually or in combination and can be conjugated to carrier molecules like CRM197 to enhance immunogenicity. The invention thus provides compositions and methods to confer protective immunity against targeted C. jejuni strains while avoiding the risks linked to LOS-induced autoimmune phenomena.
Claims Coverage
The patent contains multiple independent claims focusing on methods of inducing immune responses using isolated polysaccharides from selected Campylobacter jejuni strains, excluding lipooligosaccharide structures associated with Guillain-Barré Syndrome. The main inventive features address the selection of polysaccharide antigens, immune response specificity, and conjugation to carriers.
Method of inducing immune response using isolated capsule polysaccharides from HS50 strain
Administering an immunogenic composition comprising one or more isolated capsule polysaccharides or polysaccharide polymers derived from Campylobacter jejuni strain HS50, excluding LOS structures associated with Guillain-Barré Syndrome. The immune response targets C. jejuni strains of the HS4 complex, including HS4, HS13, HS4/13/64, and HS50, with defined polysaccharide structures and polymer length (n=1 to 100).
Method of inducing immune response from immunogenic composition derived from HS4 complex strains
Administering an immunogenic composition comprising one or more isolated capsule polysaccharides or polysaccharide polymers derived from one or more Campylobacter jejuni strains of the HS4 complex, excluding LOS structures associated with Guillain-Barré Syndrome. The response targets strain HS50, with defined structures for HS4 and HS4/13/64 and polymer length (n=1 to 100).
Method of inducing immune response using isolated polysaccharides derived from various strains
Administering an immunogenic composition comprising one or more isolated capsule polysaccharides or polysaccharide polymers derived from strains HS4, HS4/13/64, HS5, and HS50, excluding LOS structures associated with Guillain-Barré Syndrome, with specified polysaccharide structures and polymer length.
Selection of specific polysaccharide structures derived from HS50
Isolated capsule polysaccharides or polysaccharide polymers derived from Campylobacter jejuni strain HS50 include two specific structures with non-stoichiometric MeOPN substitutions at defined carbon positions, with polymer length from 1 to 100.
Linkage of isolated capsule polysaccharides to carrier molecules
The isolated capsule polysaccharides or polysaccharide polymers can be linked to a carrier molecule to improve immunity.
Carrier molecule as a protein carrier
The carrier molecule linked to the isolated polysaccharides can be a protein carrier.
Use of CRM197 as a protein carrier
The protein carrier linked to the isolated capsule polysaccharides can specifically be CRM197.
Administration protocol and dosing range
The immunogenic composition can be administered at a dose range of 0.1 μg to 10 mg per dose followed by a boosting dose within the same range.
Multiple dosing schedule
The method includes administering three doses of the immunogenic composition to the mammal within the specified dosing range.
Use of adjuvants
The immunogenic composition can comprise an adjuvant to enhance the immune response.
Selection of specific adjuvants
Adjuvants can include LTR192G, aluminum hydroxide, RC529, QS21, oligodeoxynucleotides (ODN), and aluminum phosphate.
Use of CpG-containing oligodeoxynucleotides
When oligodeoxynucleotides are used as adjuvants, they can be CpG-containing oligodeoxynucleotides.
Routes of administration
The immunogenic composition can be administered by multiple routes including orally, nasally, subcutaneously, intradermally, transdermally, transcutaneously, intramuscularly, and rectally.
The independent claims cover methods of inducing immune responses against Campylobacter jejuni strains by administering immunogenic compositions comprising isolated capsule polysaccharides or polysaccharide polymers from specific strains within the HS4 complex and others. The claims emphasize exclusion of harmful LOS structures, use of defined polysaccharide structures, options for conjugation to protein carriers such as CRM197, specified dosing regimens including boosters, inclusion of adjuvants, and varied administration routes.
Stated Advantages
The immunogenic compositions induce specific immunity against pathogenic Campylobacter jejuni strains without including lipooligosaccharide components associated with autoimmune complications like Guillain-Barré Syndrome.
Conjugation to protein carriers, such as CRM197, enhances immunogenicity of the polysaccharide antigens.
The compositions provide cross-protection within strain complexes, such as the HS4 complex, maximizing coverage against prevalent disease-causing serotypes.
The compositions can be administered by multiple routes and with various adjuvants to tailor immune responses effectively.
Documented Applications
Use as immunogenic compositions or vaccines to induce protective immunity against diarrheal disease caused by Campylobacter jejuni strains including HS1, HS44, HS5, HS13, HS4/13/64, HS50, HS3, and HS2.
Methods for immunizing mammals against specific C. jejuni strains or strain complexes by administering isolated capsule polysaccharide antigens or conjugates thereof.
Formulations for generating anti-C. jejuni immune responses avoiding autoimmune complications associated with LOS structures.
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