Antibodies against Campylobacter species
Inventors
PIZZUTO, Matteo Samuele • Benigni, Fabio • Corti, Davide • Grassi, Fabio • PERRUZZA, LISA
Assignees
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Publication Number
US-12297258-B2
Publication Date
2025-05-13
Expiration Date
Abstract
The instant disclosure provides antibodies and antigen-binding fragments thereof that are specific for Campylobacter and, in certain embodiments, are capable of neutralizing a Campylobacter infection in a subject. In certain embodiments, the antibody or antigen binding fragment comprises an IgA antibody, such as, for example, a secretory IgA antibody. Also provided are pharmaceutical compositions comprising a disclosed antibody or antigen-binding fragment. Methods of using the antibodies, antigen-binding fragments, and compositions to treat or prevent a Campylobacter infection in a subject are also provided. In certain embodiments, recombinant secretory IgA antibodies of the instant disclosure are administered orally to a subject having or at risk of developing a Campylobacter infection.
Core Innovation
The disclosure describes isolated antibodies, or antigen-binding fragments thereof, that are specific for a Campylobacter flagellum capping protein (FliD) epitope. The antibodies are defined by specified HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences according to SEQ ID NOs 9-14 or according to SEQ ID NOs 25-30, and are provided in selected immunoglobulin isotypes including IgA2, IgG, IgD, IgE, or IgM, or in selected alternative isotypes including IgA, IgD, IgE, IgG1, or IgM.
The disclosure frames the approach as targeting the flagellar capping protein FliD to limit motility and enhance clearance. It includes epitope specificity information for FliD linear versus conformational epitopes, retained binding activity in SIgA2, and binding potency using EC50 metrics measured by ELISA.
The disclosure further characterizes antibody persistence in caecum and feces, and compares immunoglobulin formats and isotypes, including IgA1 versus IgA2 and the effect of isotype conversion in which IgG reduces prophylactic activity. Exemplary anti-FliD monoclonal antibodies are characterized, including CAA1, CCG4, and HGN194, and the document supports related constructs including polynucleotides, vectors, recombinant host cells, and kits for targeting FliD linear versus conformational epitopes.
Claims Coverage
The independent claims provide coverage for two inventive features: an isolated antibody or antigen-binding fragment specific for a Campylobacter FliD epitope defined by specified heavy-chain and light-chain CDR sequence sets and allowed immunoglobulin isotypes, and a kit comprising two such antibodies with distinct CDR sets and isotypes. The coverage also includes therapeutic use and specified post-administration outcome readouts for the antibody.
Isolated antibody specific for a Campylobacter FliD epitope with defined CDR sets
An isolated antibody, or an antigen-binding fragment thereof, that is specific for a Campylobacter flagellum capping protein (FliD) epitope, wherein the antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences according to SEQ ID NOs: 9-14, respectively, and is an IgA2, IgG, IgD, IgE, or IgM isotype; or the antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences according to SEQ ID NOs: 25-30, respectively, and is an IgA, IgD, IgE, IgG1, or IgM isotype.
Kit with two antibodies defined by distinct FliD epitope CDR sets
A kit comprising a first antibody or antigen-binding fragment having HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences according to SEQ ID NOs: 9-14 and an IgA2, IgG, IgD, IgE, or IgM isotype, and a second antibody or antigen-binding fragment having HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 sequences according to SEQ ID NOs: 25-30 and an IgA, IgD, IgE, IgG1, or IgM isotype.
Across the independent claims, the inventive coverage is anchored on antibodies specific for a Campylobacter FliD epitope defined by particular HCDR/LCDR sequence sets with restricted immunoglobulin isotypes, and optionally arranged as a kit containing both antibody components. Dependent claims refine the antibodies with quantitative sequence identity thresholds and specify therapeutic administration and associated outcome measures including stool CFUs, lipocalin-2, PMN infiltration, caecum histology, and antibody presence in caecum and/or feces for at least 4 or 8 hours.
Stated Advantages
Reduces Campylobacter motility in vitro.
Provides prophylactic efficacy in an immunocompetent mouse model, including decreased CFUs over time.
Reduces inflammation markers, including lipocalin-2 (LCN2) and PMN infiltration.
Improves caecum histology.
Oral SIgA shows pharmacokinetic persistence in the gastrointestinal context versus an irrelevant control.
Reduced prophylactic activity is reported for IgG1 compared with SIgA, indicating an advantage for SIgA over IgG1 in the document’s prophylaxis readouts.
Provides antibody presence in caecum and/or feces for at least 4 hours or at least 8 hours.
Documented Applications
Prophylactic use via oral administration of rSIgA to reduce Campylobacter in an immunocompetent mouse model of Campylobacter infection, assessed by stool CFU shedding kinetics and inflammation/readouts such as LCN2, PMN infiltration, and caecum histology.
Therapeutic use is claimed as a method for treating a Campylobacter infection in a subject by administering an effective amount of the antibody or antigen-binding fragment.
Using stool sample readouts and bioinflammation-associated measures, including reduced Lipocalin-2, altered Campylobacter CFUs, reduced PMN infiltration in caecum, and improved caecum histology, following administration in mouse models.
Targeting FliD linear versus conformational epitopes as part of the disclosed applications, including kit use.
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