Biofilm disrupting antibody compositions

Abstract

Provided herein are methods and compositions for disrupting biofilms in vitro and in vivo. Also disclosed herein are antibodies comprising specific heavy chain (HC) immunoglobulin variable domain sequences and / or specific light chain (LC) immunoglobulin variable domain sequences.

Description

[0001] This application is a divisional application of the invention patent application which entered the Chinese national stage on February 28, 2022, with application number 202080061193.5, application date on July 7, 2020, and invention name “Antibody composition for destroying biofilms”.

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Application No. 63 / 033,109, filed June 1, 2020, and U.S. Provisional Application No. 62 / 871,457, filed July 8, 2019, the contents of each of which are incorporated herein by reference in their entirety.

[0004] Government Funding Statement

[0005] This invention was made with government support through the National Institute on Deafness and Other Communication Disorders (NIDCD) of the National Institutes of Health (NIH) under Grant No. R01 DC011818. The government has certain rights in this invention.

[0006] public domain

[0007] The present disclosure generally relates to methods and compositions for reducing and / or eradicating bacterial biofilms.

[0008] background

[0009] DNABII protein family is naturally present in bacterial cell outside and promotes biofilm formation.The albumen of at least one DNABII family is present in all known true bacteria.Although these proteins cause strong natural and acquired immune response, host object can not produce the immune protective antibody of antagonism family member naturally due to infection.The major problem that bacterial biofilm is relevant is that host immune system and / or antibiotic and other antimicrobial agents can not approach the bacterium that is protected in biofilm.

[0010] Biofilms also exist in industrial equipment. For example, biofilms are implicated in a variety of petroleum process problems, from oil field production to gas station storage tanks. In the field, sulfate-reducing biofilm bacteria produce hydrogen sulfide (acidic oil). In process piping, biofilm activity gradually forms slime, clogging filters and orifices. Biofilms and biofilm organisms also cause corrosion of piping and petroleum process equipment. These problems can manifest throughout oil and gas production facilities, to the point where sludge and aggressive biofilm organisms have been found on the surfaces of final product storage tanks.

[0011] Biofilms are also implicated in various water treatment processes, both domestic and industrial. They can grow on the surfaces of process equipment, hindering their performance, such as by degrading heat transfer or clogging filters and membranes. Biofilms growing on cooling tower fill can add enough weight to cause the fill to collapse. Biofilms can even cause corrosion of highly specialized stainless steel. Biofilms in water treatment can reduce the value of the end product, such as biofilm contamination in paper processing or the attachment of even a single cell to a silicon chip. Biofilms growing in drinking water distribution systems can harbor potentially pathogenic, aggressive, or bacterial organisms, reducing the sensory quality of the water. In the home, biofilms can be found in or on any surface that supports microbial growth, such as in sewers, on food preparation surfaces, in toilets, and in swimming pools and baths.

[0012] Therefore, it is necessary to disrupt the protective barrier of biofilms to treat or kill the associated bacterial infections and remove them from various surfaces and water systems.

[0013] Overview

[0014] In bacterial cells, the DNABII protein is a DNA-binding protein that necessarily bends the DNA substrate upon binding. Similarly, an exemplary substrate is DNA that is already in a bent conformation because the energy required for bending is not needed at this time.

[0015] DNABII family is the member of the protein class that is referred to as nucleoid associated proteins (nucleoid associated proteins, NAP), and they are bacterial proteins, partly shape intracellular bacterial nucleoid (Browning et al. (2010) Curr.Opin.Microbiol.13:773-780).In addition, this family is ubiquitous, is expressed by almost all true bacteria. Up to now, all family members that have been characterized all play a role with the homodimer or heterodimer of subunit.This family is divided into two types, HU (histone-like protein) and IHF (integration host factor), wherein B.cenocepacia can express these two types (bacterial strain J2315 gene: BCAL3530, hupA; BCAL1585, hupB; BCAL1487, ihfA and BCAL2949, ihfb), and many other bacteria also express HU and IHF. The main difference between these family members is that HU binds DNA in a sequence-independent manner, while IHF binds to a consensus sequence (WATCAANNNNTTR, wherein W is A or T and R is a purine, SEQ ID NO: 28) (Swinger et al. (2004) Curr. Opin. Struct. Biol. 14: 28-35). All DNABII proteins bind to DNA and significantly bend it. For example, Escherichia coli IHF can bend DNA into almost a U-shaped turn (Rice et al. (1996) Cell 87: 1295-1306). In addition, all family members prefer pre-bent or curled DNA structures, such as the Holliday junction, which is a cross-shaped structure and the center of DNA recombination. In fact, DNABII proteins function as cofactors, promoting all intracellular DNA functions, including gene expression, recombination, repair and replication (Swinger et al. (2004) Curr. Opin. Struct. Biol. 14: 28-35).

[0016] The DNABII protein family is located on the outside of bacterial cells in the biofilm state. Applicants have shown that these proteins actually bind to extracellular DNA at key branched junctions.

[0017] Thus, provided herein is an antibody or antigen-binding fragment thereof comprising, or consisting essentially of, or consisting of, a heavy chain (HC) immunoglobulin variable region sequence and / or a light chain (LC) immunoglobulin variable region sequence, wherein the HC immunoglobulin variable region comprises the sequence of amino acids (aa) 25 to aa 144 of SEQ ID NO: 13, or an equivalent thereof, or consists essentially of, or consists of, and the LC immunoglobulin variable region comprises the sequence of aa 21 to aa 132 of SEQ ID NO: 14, or an equivalent thereof, or consists essentially of, or consists of. Further provided herein is an antibody or its antigen-binding fragment, which includes a heavy chain (HC) immunoglobulin variable region sequence and / or a light chain (LC) immunoglobulin variable region sequence, or is substantially composed of, or is composed of, the HC immunoglobulin variable region includes a sequence selected from SEQ ID NO:13, aa25 to aa 144 of 24 or 26 or its each equivalent, or is substantially composed of, or is composed of, the LC immunoglobulin variable region includes a sequence selected from SEQ ID NO:14 or 25 aa 21 to aa 132, SEQ ID NO:27 aa 21 to aa 126 or its each equivalent, or is substantially composed of, or is composed of. In certain embodiments, the antibody or its fragment binds to a DNABII peptide (e.g., a head region (tip region) of a DNABII peptide, including but not limited to: a head region of IHF or HU, a head region of IHFA or IHFB and / or a head chimeric peptide IhfA5-mIhfB4 NTHI and / or the tail region of a DNABII peptide, including but not limited to the tail region of IHF or HU, the tail region of IHFA or IHFB and / or the tail chimeric peptide IhfA3-IhfB2 NTHI In one embodiment, the antibody or fragment thereof binds to the head chimeric peptide IhfA5-mIhfB4 NTHI or tail chimeric peptide IhfA3-IhfB2 NTHI .

[0018] Also provided herein is an antibody or its antigen-binding fragment, which includes a heavy chain (HC) immunoglobulin variable region sequence and / or a light chain (LC) immunoglobulin variable region sequence, or is substantially composed of, or is composed of, the HC immunoglobulin variable region includes a sequence selected from SEQ ID NO:13 or 24 aa 25 to aa 144 or its equivalent of each, or is substantially composed of, or is composed of, the LC immunoglobulin variable region includes a sequence selected from SEQ ID NO:14 or 25 aa 21 to aa 132 or its equivalent of each, or is substantially composed of, or is composed of. In certain embodiments, the antibody or its fragment binds to the head region of DNABII peptide (e.g., DNABII peptide, including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB and / or the head chimeric peptide IhfA5-mIhfB4 NTHI In one embodiment, the antibody or fragment thereof binds to the head chimeric peptide IhfA5-mIhfB4 NTHI .

[0019] Further provided herein is an antibody or its antigen-binding fragment, which includes a heavy chain (HC) immunoglobulin variable region sequence and / or a light chain (LC) immunoglobulin variable region sequence, or consisting essentially of, or consisting of, the HC immunoglobulin variable region includes a sequence selected from SEQ ID NO:1-6, 24 or 26 aa 25 to aa 144 or its equivalent of each, or consisting essentially of, or consisting of, the LC immunoglobulin variable region includes a sequence selected from SEQ ID NO:7-9 or 25 aa 21 to aa 132, SEQ ID NO:10-12 or 27 aa 21 to aa126 or its equivalent of each, or consisting essentially of, or consisting of. In certain embodiments, the antibody or its fragment binds to the head region of DNABII peptide (e.g., DNABII peptide, including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB and / or the head chimeric peptide IhfA5-mIhfB4 NTHI and / or the tail region of a DNABII peptide, including but not limited to: the tail region of IHF or HU, the tail region of IHFA or IHFB and / or the tail chimeric peptide IhfA3-IhfB2 NTHI In one embodiment, the antibody or fragment thereof binds to the head chimeric peptide IhfA5-mIhfB4 NTHI or tail chimeric peptide IhfA3-IhfB2 NTHI .

[0020] Further provided herein is an antibody or antigen-binding fragment thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable region sequence and / or a light chain (LC) immunoglobulin variable region sequence, wherein the HC immunoglobulin variable region comprises, consists essentially of, or consists of a sequence selected from aa 25 to aa 473 of SEQ ID NO: 1-6, 13, 24 or 26, or an equivalent of each thereof, and / or the LC immunoglobulin variable region comprises, consists essentially of, or consists of a sequence selected from aa 21 to aa 239 of SEQ ID NO: 7-9, 14 or 25, aa 21 to aa 233 of SEQ ID NO: 10-12 or 27, or an equivalent of each thereof. In certain embodiments, the antibody or fragment thereof binds to a DNABII peptide (e.g., a head region of a DNABII peptide, including but not limited to: a head region of IHF or HU, a head region of IHFA or IHFB, and / or a head chimeric peptide IhfA5-mIhfB4 NTHI and / or the tail region of a DNABII peptide, including but not limited to: the tail region of IHF or HU, the tail region of IHFA or IHFB and / or the tail chimeric peptide IhfA3-IhfB2 NTHI In one embodiment, the antibody or fragment thereof binds to the head chimeric peptide IhfA5-mIhfB4 NTHI or tail chimeric peptide IhfA3-IhfB2 NTHI .

[0021] A kind of antibody or its antigen-binding fragment is provided herein in addition, it includes following CDR sequence, or is substantially made up of it, or is made up of it: be selected from SEQ ID NO:1-6,13,24 or 26 or the sequence of its each equivalent any one, any two or all three CDR; And / or be selected from SEQ ID NO:7-12,14,25 or 27 or the sequence of its each equivalent any one, any two or all three CDR.In certain embodiments, described antibody or its fragment combines DNABII peptide (for example DNABII peptide head region, include but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB and / or head chimeric peptide IhfA5-mIhfB4 NTHI and / or the tail region of a DNABII peptide, including but not limited to: the tail region of IHF or HU, the tail region of IHFA or IHFB and / or the tail chimeric peptide IhfA3-IhfB2 NTHI In one embodiment, the antibody or fragment thereof binds to the head chimeric peptide IhfA5-mIhfB4 NTHI or tail chimeric peptide IhfA3-IhfB2 NTHI .

[0022] Non-limiting examples of antigen binding fragments are selected from Fab, F(ab')2, Fab', scFv or Fv.

[0023] In another aspect, the present invention provides a Fab fragment of the antibody, wherein the antibody specifically binds to the head region of the DNABII peptide (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB and / or the head chimeric peptide IhfA5-mIhfB4 NTHI ). Also provided herein are fragments of the antibodies disclosed herein. In one embodiment, the fragment is an antigen-binding fragment selected from Fab, F(ab')2, Fab', scFv or Fv. In another embodiment, the fragment specifically binds to the head region of the DNABII peptide.

[0024] Also provided herein are formulations comprising the Fab fragments.

[0025] In another aspect, the antibody or fragment thereof is modified. Non-limiting examples of modifications include PEGylation, PEG mimetic, polysialylation, HESylation, or glycosylation.

[0026] The antibodies and antigen-binding fragments may be detectably labeled, or include a detectable label and / or a purification marker.

[0027] Also provided herein are polypeptides comprising, consisting essentially of, or consisting of the complementary determining regions (CDRs) of the antibodies or antigen-binding fragments or regions disclosed above. The CDRs may be selected from CDR1, CDR2, or CDR3. The CDRs may be detectably labeled or include a detectable marker and / or a purification marker.

[0028] Further provided herein are isolated polypeptides, wherein the polypeptide comprises, consists essentially of, or consists of an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-14 or 24-27; amino acids (aa) 25 to aa 144 of SEQ ID NOs: 1-6, 13, 24, or 26; aa 21 to aa 132 of SEQ ID NOs: 7-9, 14, or 25; aa 21 to aa 126 of SEQ ID NOs: 10-12 or 27; or equivalents of each thereof. Also provided herein are isolated polypeptides comprising, consisting essentially of, or consisting of an amino acid sequence of one or more antibodies or fragments thereof disclosed herein. The polypeptides may be detectably labeled and / or include a detectable marker and / or a purification marker. In another embodiment, the polypeptide further comprises a signal peptide.

[0029] Further provided herein are isolated polynucleotides encoding antibodies or their antigen-binding fragments, the CDRs of the antigen-binding fragments or antibodies, the polypeptides or their equivalents of each, which are optionally operably linked to promoters and / or enhancer elements. The polynucleotides may be detectably labeled and / or include detectable markers and / or purification markers. The polynucleotides may further include a signal peptide polynucleotide sequence upstream of the immunoglobulin variable region of the antibody. They may be contained in a vector and / or a host cell. Therefore, further provided herein is a vector comprising the isolated polynucleotides disclosed herein, or consisting essentially of them, or consisting of them. Such a vector may be a plasmid or a viral vector, optionally selected from retroviral vectors, lentiviral vectors, adenoviral vectors and adeno-associated viral vectors. Also provided herein is a host cell comprising one or more polynucleotides and / or vectors disclosed herein.

[0030] Further provided herein are compositions comprising a carrier and one or more of the following: an antibody or fragment thereof, a CDR, a polypeptide, an isolated polynucleotide, a vector, or a host cell, or consisting essentially of the same, or consisting of the same. In one embodiment, the carrier is a pharmaceutically acceptable carrier. Additionally or alternatively, the carrier is a solid phase carrier or a solid support. In another embodiment, the carrier is suitable for use in an industrial environment. Also provided herein are non-physiological surfaces coated with an antibody or fragment thereof as disclosed herein. In one embodiment, the surface is in an industrial environment. In certain embodiments, the fragment is an antigen binding fragment.

[0031] Also provided herein are methods for producing the antibodies, fragments, CDRs, or polypeptides, comprising, consisting essentially of, or consisting of the following steps: culturing a host cell comprising a polynucleotide encoding the antibody, antigen-binding fragment, polypeptide, or CDR under conditions for expressing the polynucleotide, and optionally isolating the antibody, fragment, CDR, and / or polypeptide from the cell and / or culture. In one embodiment, the host cell is a mammalian cell.

[0032] In one aspect, the present invention provides a method for inhibiting or competing for DNABII polypeptide or protein binding to microbial DNA. The method comprises the following steps, or is essentially composed of it, or is composed of it: contacting the DANBII polypeptide or protein with one or more antibodies, fragments thereof, polypeptides or CDRs disclosed herein. In one embodiment, the antibody, fragment or CDR binds to the head region of the DNABII peptide (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB and / or the head chimeric peptide IhfA5-mIhfB4 NTHIIn a further embodiment, the antibody, fragment, polypeptide or CDR thereof binds to the head chimeric peptide IhfA5-mIhfB4 NTHI In further embodiments, the contacting is performed in vivo or in vitro.

[0033] In another aspect, the present invention provides a method for destroying a biofilm. The method comprises the following steps, or is substantially composed of it, or is composed of it: the biofilm is contacted with one or more antibodies disclosed herein, its fragment, polypeptide or CDR. In one embodiment, the antibody, its fragment or CDR binds to the head region of the DNABII peptide (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB and / or the head chimeric peptide IhfA5-mIhfB4 NTHI In a further embodiment, the antibody, fragment, polypeptide or CDR thereof binds to the head chimeric peptide IhfA5-mIhfB4 NTHI In further embodiments, the contacting is performed in vivo or in vitro.

[0034] Also provided herein are methods for preventing biofilm formation on a surface or methods for disrupting a biofilm on a surface, the methods comprising, consisting essentially of, or consisting of treating a surface susceptible to or containing a biofilm with, for example, one or more antibodies, antigen-binding fragments, polypeptides, or CDRs disclosed herein, wherein the antibodies, fragments, polypeptides, or CDRs bind to the head region of a DNABII peptide (including but not limited to, the head region of IHF or HU, the head region of IHFA or IHFB, and / or the head chimeric peptide IhfA5-mIhfB4). NTHI In a further embodiment, the antibody, fragment, polypeptide or CDR thereof binds to the head chimeric peptide IhfA5-mIhfB4 NTHI In further embodiments, the treatment is performed in vivo or in vitro.

[0035] Also provided herein is a method for detecting biofilm on a surface, the method comprising, consisting essentially of, or consisting of the following steps: contacting the surface (in one aspect, the surface is susceptible to or comprises a biofilm) with one or more antibodies, antigen-binding fragments, polypeptides, or CDRs disclosed herein, wherein the antibody, fragment, polypeptide, or CDR binds to the head region of a DNABII peptide (including but not limited to the head region of IHF or HU, the head region of IHFA or IHFB, and / or the head chimeric peptide IhfA5-mIhfB4); NTHI In a further embodiment, the antibody, fragment, polypeptide or CDR thereof binds to the head chimeric peptide IhfA5-mIhfB4 NTHI In further embodiments, the contacting is performed in vivo or in vitro.

[0036] In one aspect, the present invention provides a method for detecting the microbial infection that produces biofilm in object.The method comprises the following steps, or is substantially composed of it, or is composed of it: the biological sample that the suspicion that comprises biofilm separated from the object is contacted with one or more antibodies, Fab, polypeptide or CDR disclosed herein, and the combination of the antibody, Fab, polypeptide or CDR described in the test sample with any biofilm.Consumption can be determined by a treating doctor or veterinarian, for example, to the effective amount of this object.In one embodiment, the antibody, its fragment, polypeptide or CDR is in conjunction with the tail region or the head region of DNABII peptide (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB, the head chimeric peptide IhfA5-mIhfB4 NTHI , the tail region of IHF or HU, the tail region of IHFA or IHFB and / or the tail chimeric peptide IhfA3-IhfB2 NTHI In a further embodiment, the contacting is performed in vivo or in vitro.

[0037] In yet another aspect, a method for screening an object with a biofilm is provided herein, the method comprising the following steps, or substantially consisting of, or consisting of: the biological sample comprising the biofilm to be separated from the object is contacted with one or more antibodies, fragments thereof, polypeptides or CDRs disclosed herein, and the combination of the antibody, fragments thereof, polypeptides or CDRs with any biofilm in the test sample. In one embodiment, the antibody, fragments thereof, polypeptides or CDRs are in conjunction with the tail region or head region of the DNABII peptide (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB, the head chimeric peptide IhfA5-mIhfB4 NTHI , the tail region of IHF or HU, the tail region of IHFA or IHFB and / or the tail chimeric peptide IhfA3-IhfB2 NTHI In a further embodiment, the subject detected for said binding is selected to be administered one or more antibodies, fragments thereof, polypeptides or CDRs disclosed herein, and / or one or more polynucleotides or vectors encoding said antibodies, fragments thereof, polypeptides or CDRs, wherein said antibodies, fragments thereof, polypeptides or CDRs bind to the head region of the DNABII peptide (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB and / or the head chimeric peptide IhfA5-mIhfB4 NTHI The dosage can be determined by the treating physician or veterinarian, for example, an amount effective for the subject. In further embodiments, the contacting is performed in vivo or in vitro.

[0038] Provided herein is a method for detecting biofilm in an object, by administering one or more antibodies disclosed herein or its fragment and detecting any combination of an antibody, its fragment, polypeptide or CDR disclosed herein with a biofilm to the object. In one aspect, the antibody, its fragment, polypeptide or CDR binds to the tail region or head region of a DNABII peptide (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB, the head chimeric peptide IhfA5-mIhfB4 NTHI , the tail region of IHF or HU, the tail region of IHFA or IHFB and / or the tail chimeric peptide IhfA3-IhfB2 NTHI In another embodiment, the method further comprises detecting the binding of the antibody, fragment, polypeptide or CDR thereof to a biological membrane.

[0039] In one aspect, provided herein are methods for preventing or destroying biofilms in a subject, comprising, consisting essentially of, or consisting of the following steps: administering to the subject one or more antibodies, fragments thereof, polypeptides, or CDRs disclosed herein, and / or one or more polynucleotides or vectors encoding said antibodies, fragments thereof, polypeptides, or CDRs, wherein these bind to the head region of a DNABII peptide (including but not limited to the head region of IHF or HU, the head region of IHFA or IHFB, and / or the head chimeric peptide IhfA5-mIhfB4). NTHI ). The dosage can be determined by the treating physician or veterinarian, for example, an amount effective for the subject. In one embodiment, the method further comprises detecting a biofilm: contacting one or more antibodies, fragments thereof, polypeptides or CDRs disclosed herein with a sample suspected of containing a biofilm and detecting binding of the biofilm to the antibody, fragment thereof, polypeptide or CDR, wherein the antibody, fragment thereof, polypeptide or CDR binds to the tail region or head region of the DNABII peptide (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB, the head chimeric peptide IhfA5-mIhfB4 NTHI , the tail region of IHF or HU, the tail region of IHFA or IHFB and / or the tail chimeric peptide IhfA3-IhfB2 NTHI ).

[0040] In another aspect, provided herein are methods for inhibiting, preventing, or treating a microbial infection that produces a biofilm in a subject, the method comprising, consisting essentially of, or consisting of: administering to the subject one or more antibodies, fragments thereof, polypeptides, or CDRs disclosed herein, and / or one or more polynucleotides or vectors encoding the antibodies, fragments thereof, polypeptides, or CDRs, wherein these bind to the head region of the DNABII peptide (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB, and / or the head chimeric peptide IhfA5-mIhfB4). NTHI ). The dosage can be determined by the treating physician or veterinarian, for example, an amount effective for the subject. In one embodiment, the method further comprises detecting a biofilm: contacting one or more antibodies, fragments thereof, polypeptides or CDRs disclosed herein with a sample suspected of containing a biofilm and detecting binding of the biofilm to the antibody, fragment thereof, polypeptide or CDR, wherein the antibody, fragment thereof, polypeptide or CDR binds to the tail region or head region of the DNABII peptide (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB, the head chimeric peptide IhfA5-mIhfB4 NTHI , the tail region of IHF or HU, the tail region of IHFA or IHFB and / or the tail chimeric peptide IhfA3-IhfB2 NTHI ).

[0041] In another aspect, provided herein is a method for preventing or treating a condition characterized by biofilm formation in a subject by administering to the subject one or more antibodies, fragments thereof, polypeptides or CDRs disclosed herein, and / or one or more polynucleotides or vectors encoding said antibodies, fragments thereof, polypeptides or CDRs, wherein said polynucleotides or vectors bind to the head region of a DNABII peptide (including but not limited to the head region of IHF or HU, the head region of IHFA or IHFB and / or the head chimeric peptide IhfA5-mIhfB4). NTHIThe dosage can be determined by the treating physician or veterinarian, for example, an amount effective for the subject. Non-limiting examples of conditions include chronic non-healing wounds, lung infections caused by Burkholderia sp., venous ulcers, diabetic foot ulcers, ear infections, sinus infections, urinary tract infections, gastrointestinal diseases, hospital-acquired pneumonia, ventilator-associated pneumonia, surgical implant-related infections, lung infections, respiratory tract infections, cystic fibrosis, chronic obstructive pulmonary disease, catheter-related infections, indwelling device-related infections, implant-related infections, osteomyelitis, cellulitis, abscesses, and periodontal disease. In one embodiment, the method further comprises detecting a biofilm by contacting one or more antibodies, fragments thereof, polypeptides or CDRs disclosed herein with a sample suspected of containing a biofilm and detecting binding of the biofilm to the antibody, fragment thereof, polypeptide or CDR, wherein the antibody, fragment thereof, polypeptide or CDR binds to the tail region or head region of the DNABII peptide (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB, the head chimeric peptide IhfA5-mIhfB4 NTHI , the tail region of IHF or HU, the tail region of IHFA or IHFB and / or the tail chimeric peptide IhfA3-IhfB2 NTHI ).

[0042] In certain embodiments of the methods disclosed herein, administration of one or more of the antibodies, fragments thereof, polypeptides, or CDRs reduces one or more proinflammatory cytokines in a subject. Non-limiting examples of proinflammatory cytokines include IL-1β, IL6, IL8, IL12p70, IL17A, interferon (IFN), and tumor necrosis factor (TFN). Additionally or alternatively, administration of one or more of the antibodies, fragments thereof, polypeptides, or CDRs increases one or more anti-inflammatory cytokines in a subject. In one embodiment, anti-inflammatory cytokines include, but are not limited to, IL10, IL 13, IL-1ra, IL-

[0043] 4. IL-11 and transforming growth factor-β (TGF-β).

[0044] Also provided herein is a method of conferring passive immunity in a subject, the method comprising, consisting essentially of, or consisting of the following steps: administering to the subject one or more antibodies, fragments thereof, polypeptides, or CDRs disclosed herein, and / or one or more polynucleotides or vectors encoding the antibodies, fragments thereof, polypeptides, or CDRs, wherein the antibodies, fragments thereof, polypeptides, or CDRs bind to the head region of a DNABII peptide (including but not limited to the head region of IHF or HU, the head region of IHFA or IHFB, and / or the head chimeric peptide IhfA5-mIhfB4). NTHIThe dosage can be determined by the treating physician or veterinarian, for example, an amount effective for the subject.

[0045] In one aspect, therapeutic methods are combined with diagnostic methods to detect and / or monitor biofilm formation and disruption using the antibodies, fragments, polypeptides, or CDRs disclosed herein.

[0046] In certain embodiments, the biofilm is derived from (i.e., produced from) Gram-negative or Gram-positive biofilm bacteria. In certain embodiments, the biofilm comprises DNABII protein. In a further embodiment, the biofilm comprises histone-like protein (HU) or integration host factor (IHF) binding protein from Escherichia coli U93. In certain embodiments, the DNABII peptide is an IHF peptide. In addition or alternatively, the DNABII peptide is a HU peptide. In certain embodiments, the head region of the DNABII peptide is the head region of IHFA and / or the head region of IHFB. In a further embodiment, the head region of the DNABII peptide is the IHFA head region directly or indirectly (such as through a connector) coupled to the IHFB head region. In a further embodiment, the head region of the DNABII peptide is IhfA5-mIhfB4 NTHI Head chimeric peptide. In certain embodiments, the tail region of the DNABII peptide is the tail region of IHFA and / or the tail region of IHFB. In further embodiments, the tail region of the DNABII peptide is the IHFA tail region coupled directly or indirectly (e.g., via a linker) to the IHFB tail region. In further embodiments, the tail region of the DNABII peptide is IhfA3-IhfB2 NTHI Tail chimeric peptide.

[0047] Further provided herein is a method for preparing an interfering nucleic acid, comprising, consisting essentially of, or consisting of the steps of preparing a nucleic acid consisting of about 10-20 nucleotides that specifically binds to a specific binding partner of an antibody or fragment thereof disclosed herein, and optionally isolating the interfering nucleic acid prepared by the method.

[0048] In another aspect, provided herein is a non-physiological surface covered with one or more antibodies, fragments thereof, polypeptides or CDRs disclosed herein, and optionally, wherein in one aspect, the surface is in an industrial setting.

[0049] Also provided herein are methods of obtaining antiserum effective for disrupting biofilms, comprising immunizing a subject with a small molecule, and recovering antiserum from the subject, and optionally isolating polyclonal antiserum or monoclonal antibodies from the subject.

[0050] Also provided herein are kits comprising one or more antibodies, fragments thereof, polypeptides, CDRs, polynucleotides, vectors, host cells, or compositions disclosed herein, and optionally, instructions for use. BRIEF DESCRIPTION OF THE DRAWINGS

[0052] Figure 1 Provided are diagrams showing how DNABII protein (such as IHF) binds to double-stranded DNA and the two arms of the DNABII protein.

[0053] Figures 2A to 2D show the results of direct binding ELISAs performed to evaluate the binding of humanized monoclonal antibody variants to the corresponding peptides. The head or tail chimeric peptide was coated onto a 96-well plate at 2 μg / mL and an 8-point dilution series of antibody was added (starting at 50 μg / mL, 1:3 dilution). Anti-human IgG Fc HRP-conjugated antibody (1:7000, Jackson ImmunoResearch Laboratories, 109-035-098) was used as the secondary detection antibody. The standard direct ELISA protocol was followed and the absorbance at 450 nm was read using a microplate reader. EC was calculated. 50 values ​​and determined that the humanized variants had comparable binding. Figures 2A and 2B Humanized head chimeric peptide antibody is shown in FIG. Figures 2C and 2D Humanized tail chimeric peptide antibody is shown in FIG.

[0054] Figure 3 is an in vitro model for reversal of established biofilms in 8-well chamber slides using humanized head or tail chimeric peptide monoclonal antibodies of the present disclosure.

[0055] Figures 4A to 4G Provides a chimeric peptide IhfA5-mIhfB4 designed for targeting the head NTHI Comparison of amino acid identities between the heavy and light chains of humanized monoclonal antibodies (see Figure 4A , for detailed comparison see Figures 4B to 4G NCBI blastp was used for amino acid alignment.

[0056] Figures 5A to 5G Provided are chimeric peptides designed for targeting the tail IhfA3-IhfB2 NTHI Comparison of amino acid identities between the heavy and light chains of humanized monoclonal antibodies (see Figure 5A , for detailed comparison see Figures 5B to 5G NCBI blastp was used for amino acid alignment.

[0057] Figure 6 Provided are methods designed to target IhfA5-mIhfB4 NTHIRelative biofilm disruption data of humanized monoclonal antibodies to head chimeric peptides. Biofilm disruption: NTHI 86-028NP colonies were collected from overnight cultures on chocolate agar and suspended in brain heart infusion broth (sBHI) supplemented with 2μg β-NAD and heme / ml medium. The optical density at 490nm was then adjusted to 0.65, and the culture was diluted 1:6 in sBHI and then incubated for 3 hours at 37°C and 5% CO2. Next, the culture was diluted 1:2500 in fresh sBHI, and 200μl of the suspension was aliquoted into each well of an 8-well chamber slide. The slides were then incubated for 3 hours at 37°C and 5% CO2. After 16 hours, 200μl of fresh sBHI was added to each well, and the slides were incubated for an additional 8 hours. At this time, the medium was aspirated from each well and 5μg of monoclonal antibody was added to each well. The biofilms were incubated for an additional 16 hours. The biofilms were then washed and stained with FM1-43FX bacterial cell membrane dye (Invitrogen) and fixed overnight at 4°C in 0.1 M phosphate buffer (pH 7.4) containing 16% paraformaldehyde, 2.5% glutaraldehyde, and 4.0% acetic acid. The fixative was aspirated and 200 μl of Hank's balanced salt solution was added to each well, and the biofilms were then observed on a Zeiss 800 Meta laser scanning confocal microscope. Images were compiled using Zeiss Zen Black software, and biofilm biomass was calculated using COMSTAT 2.1 software. IhfA5-mIhfB4 NTHI K of the head chimeric peptide A (unit is 1 / M) is about 4E+05 to about 2E+08.

[0058] Figure 7 Provided are methods for using a method designed to target IhfA3-IhfB2 NTHI Relative biofilm disruption data for humanized monoclonal antibodies against chimeric peptide tails. Biofilm disruption: NTHI 86- was collected from overnight cultures on chocolate agar.

[0059] 028NP colonies were isolated and suspended in brain heart infusion broth (sBHI) supplemented with 2 μg β-NAD and heme / ml medium. The optical density at 490 nm was then adjusted to 0.65, and the culture was diluted 1:6 in sBHI and incubated at 37°C and 5% CO2 for 3 hours. Next, the culture was diluted 1:2500 in fresh sBHI, and 200 μl of the suspension was aliquoted into each well of an 8-well chamber slide. The slides were then incubated at 37°C and 5% CO2 for 3 hours. After 16 hours, 200 μl of fresh sBHI was added to each well, and the slides were incubated for an additional 8 hours. At this time, the medium was aspirated from each well, and 5 μg of monoclonal antibody was added to each well. The biofilms were incubated for an additional 16 hours. The biofilms were then washed and stained with FM1-43FX bacterial membrane stain (Invitrogen) and fixed overnight at 4°C in 0.1 M phosphate buffer (pH 7.4) containing 16% paraformaldehyde, 2.5% glutaraldehyde, and 4.0% acetic acid. The fixative was aspirated and 200 μl of Hank's balanced salt solution was added to each well, and the biofilms were then observed on a Zeiss 800 Meta laser scanning confocal microscope. Images were compiled using Zeiss ZenBlack software, and biofilm biomass was calculated using COMSTAT 2.1 software. IhfA3-IhfB2 NTHI K of the tail chimeric peptide A (unit is 1 / M) is about 8E+06 to about 2E+09.

[0060] Figure 8A to 8B show that the Fab fragment derived from the mouse monoclonal antibody targeting the β head destroys the biofilm formed by five human pathogens in vitro. Figure 8A shows a representative image of bacterial biofilm (false color white), revealing that 170nM complete IgG or Fab for the β-head domain of IHF significantly destroys biofilm. Orthogonal projection shows a top view, to depict the spatial distribution of biofilm in the xy plane, and the side view represents the biofilm height (arrow) in the z plane. Scale bar, 20 μm. Figure 8B shows the biomass in each image quantified by COMSTAT2 software. Each assay was repeated 3 times on different days, and means ± SEM are shown. *P≤0.05,

[0061] **P≤0.01 compared to the respective intact IgG or Fab (one-way ANOVA with multiple comparisons).

[0062] Figures 9A to 9D show the eradication of biofilm-resident NTHI and the decomposition of mucosal biofilm from the middle ear mediated by the mouse monoclonal antibody β-head Fab. Figure 9A shows the study schedule and the treatment given. A dose of 342nM Fab was delivered to each middle ear. Figure 9B shows the relative amount of NTHI within the mucosal biofilm and adhered to the middle ear mucosa in the treatment group. Figure 9C shows the relative mucosal biofilm score determined in the treatment group by six evaluators who were blind to the treatment. Figures 9B and 9C: 6-8 middle ears per group, showing the values ​​of a single ear and the average value of the group, and the groups in each figure are isotype control Fab, β-tail Fab and β-head Fab from left to right. *P≤0.05,

[0063] **P≤0.01, ***P≤0.001 (one-way ANOVA with multiple comparisons). Figure 9D shows representative images of chinchilla middle ears from each group, with the average mucosal biofilm score for the ear indicated in the lower right box. TM, tympanic membrane; S, bony septum; MEM, middle ear mucosa; B, biofilm (circles). In one embodiment, delivery of murine monoclonal antibody β-head Fab not only significantly reduced bacterial load in the middle ear but also eradicated mucosal biofilm, whereas β-tail Fab not only failed to do so but was associated with significant inflammation.

[0064] Figures 10A to 10B show the main proinflammatory cytokines in the middle ear fluid of animals treated with 342nM mouse monoclonal antibody-derived β-tail Fab. Figure 10A shows the relative amounts of proinflammatory cytokines in the middle ear fluid of chinchillas after NTHI stimulation and Fab fragment treatment, as determined by flow cytometric bead microarray. *P≤0.05, **P≤0.01, both compared to β-head Fab (one-way ANOVA with multiple comparisons), Compared to isotype control Fab (unpaired t-test). Figure 10B shows the relative mean concentrations of the anti-inflammatory cytokine IL-10 in the three Fab fragment treatment groups. *P≤0.05vs.β-head Fab, ++P≤0.01vs.β-tail Fabs or isotype control Fab (one-way ANOVA with multiple comparisons). 5-7 middle ear fluids were tested in each group. The average cytokine concentrations ± SD are shown. For either figure (Figure 10A or 10B), the cytokine results for the isotype control Fab, β-tail Fab, and β-head Fab groups are shown from left to right. In one embodiment, the delivery of β-head Fab results in a significant decrease in the concentrations of 6 proinflammatory cytokines and a significant increase in the concentration of the anti-inflammatory cytokine IL-10, which supports the relative inflammation or lack of inflammation shown in Figure 9D.

[0065] Figure 11A to 11D provide the eradication of the resident NTHI of the biofilm of the head chimeric Fab mediation from polyclonal rabbit IgG, the eradication of the mucosal biofilm of establishment and the disappearance of experimental disease.Figure 11A shows the research timeline.A dose of 342nMFab is delivered to each middle ear.Figure 11B shows the NTHI of the relative amount that resides in the mucosal biofilm and adheres to the middle ear mucosa after completing antibody treatment 1 or 7 days.Figure 11C shows the relative amount of the remaining mucosal biofilm determined by six evaluators who do not know the treatment provided.Figure 11B and 11C: 6 middle ears in each group, the value of single ear and the mean value of each group are shown.The group from left to right of each drawing is initial serum Fab, tail chimeric Fab and head chimeric Fab.*P≤0.05,**P≤0.01,***P≤0.001 (single factor analysis of variance with multiple comparisons).Figure 11D shows the representative images of the middle ear mucosal biofilm; Average mucosal biofilm score is shown in the lower right corner box. TM, tympanic membrane; S, bony diaphragm; MEM, middle ear mucosa; B, biofilm (circle). Rabbit polyclonal antibody Fab directed against the head chimeric peptide mediated the rapid and lasting removal of biofilm-retaining NTHI, eradicated established mucosal biofilm and resolved experimental OM. Rabbit polyclonal antibody Fab directed against the tail chimeric peptide did not induce the removal or disease regression of biofilm-retaining NTHI, but was associated with significant inflammation (Figure 11 D), as was the case with those mouse monoclonal antibody Fab directed against the β tail (see Figure 9 D).

[0066] Figures 12A to 12B Humanized head chimeric peptide monoclonal antibodies were shown to disrupt bacterial biofilms in vitro. Figure 12A Representative images of bacterial biofilms (false-colored white) after 16 hours of incubation with HuTipMab or HuTailMab are shown. Orthogonal projections show top views to depict the spatial distribution of biofilms in the xy plane, and side views represent biofilm height in the z plane (arrows). Scale bar, 20 μm. As used herein, the term "HuTipMab" refers to a monoclonal antibody (Mab or mAb) comprising an anti-head HCl having the amino acid sequence of SEQ ID NO: 1 and an anti-head LC1 having the amino acid sequence of SEQ ID NO: 7. Figure 12BShown are the percentages of biofilm biomass remaining after exposure to HuTipMab compared to HuTailMab, as determined by COMSTAT2 analysis. Mean ± SD is shown. Three experiments were performed on different days. ***P ≤ 0.001 (unpaired t-test). HuTipMab significantly destroyed biofilms formed by various respiratory pathogens in vitro. As used herein, the term "HuTailMab" refers to a monoclonal antibody (Mab or mAb) comprising an anti-tail HCl having the amino acid sequence of SEQ ID NO: 4 and an anti-tail LC1 having the amino acid sequence of SEQ ID NO: 10.

[0067] Figure 13 A to 13D are presented during the OM period of experimental NTHI induction, and the humanized monoclonal antibody (HuTipMab) for the head chimeric peptide decomposes the pre-existing NTHI biofilm in the middle ear. Figure 13 A shows the study timeline and treatment. Figure 13 B shows the relative amount of NTHI in the middle ear. Figure 13 C shows the relative amount of NTHI mucosal biofilm retained in the middle ear after treatment with human monoclonal antibodies. Figure 13 B and 13C: six middle ears in each group, showing the value of a single ear and the mean value of the group. The group from left to right in each figure is saline, humanized monoclonal antibody against tail chimeric peptide and humanized monoclonal antibody against head chimeric peptide. ****P≤0.0001 (one-way analysis of variance with multiple comparisons). Figure 13 D provides representative images of the middle ear from each group; the average mucosal biofilm score of the ear shown in the lower right corner box. S, bony diaphragm; MEM, middle ear mucosa; B, biofilm (circle). HuTipMab eradicated NTHI by disintegrating the mucosal biofilm, a rapid and sustained effect. It is also noteworthy that after humanization, the monoclonal antibody against the chimeric peptide tail was no longer associated with significant inflammatory changes, which was consistently observed with the mouse monoclonal antibody against the β tail (see Figure 9D) or the rabbit polyclonal antibody Fab against the chimeric peptide tail (see Figure 11D).

[0068] Figure 14 A to 14B shows that the proinflammatory cytokine in the middle ear fluid of the animal processed with HuTipMab significantly reduces.After flow cytometric bead microarray determination NTHI excites, NTHI excites after 6 days with humanized monoclonal antibody treatment after (Figure 14 A, after treatment is completed 1 day) and NTHI excites after 13 days with humanized monoclonal antibody treatment after (Figure 14 B, after treatment is completed 7 days), the relative amount of proinflammatory and anti-inflammatory cytokines in the middle ear fluid of chinchilla.

[0069] *P≤0·05 versus saline, **P≤0·01 versus saline, ***P≤0·001 versus saline,

[0070] ****P≤0·0001 vs. saline, +P≤0·05 vs. HuTailMab, ++P≤0·01 vs. HuTailMab,

[0071] ++P ≤ 0.001 vs. HuTailMab, ++++P ≤ 0.0001 vs. HuTailMab (one-way ANOVA with multiple comparisons). Three to five middle ear fluids were tested per group. Mean cytokine concentrations ± SD are shown. Proinflammatory cytokine levels in animals treated with HuTailMab were now comparable to those in animals treated with saline, supporting the lack of association with this now humanized monoclonal antibody compared to the murine monoclonal antibody.

[0072] Figures 15A to 15D show that immunization with the head chimeric peptide in the virus-bacteria co-infection model prevented the ascending of experimental OM. Figure 15A is a study schedule and the vaccine formulation delivered. Figure 15B is the relative amount of NTHI in the nasopharyngeal lavage fluid after bacterial stimulation for one day, to ensure that bacteria are equally colonized in all groups. 8 lavage fluids per group, NS, no significance, one-way ANOVA. Figure 15C shows that many animals in each group have signs of experimental OM, i.e. inflammation and / or middle ear fluid, observed by video otoscopy of the blinded experimenter. 8 animals per group, ****P≤0.001 contrast dmlT or tail chimeric peptide, Mantel-Cox test. Figure 15D shows representative images of the tympanic membrane from each group on the 11th day, with the highest disease incidence in the group immunized with the head chimeric peptide on this day. TM, tympanic membrane. Immunization with the head chimeric peptide can prevent the development of polymicrobial OM and promote the rapid regression of the limited disease observed.

[0073] Detailed description

[0074] Unless otherwise defined, all technical and scientific terms used herein have the same meanings as those generally understood by those of ordinary skill in the art to which the present disclosure pertains. All nucleotide sequences provided herein are presented in a 5' to 3' direction. Although any methods and materials similar or equivalent to those described herein may be used for the practice or testing of the present disclosure, specific, non-restrictive exemplary methods, devices and materials are now described. All technologies and patent publications cited herein are incorporated herein by reference in their entirety. Nothing herein should be construed as admitting that the present disclosure is not entitled to precede such disclosures due to prior inventions.

[0075] Unless otherwise indicated, the practice of the present disclosure will employ conventional techniques of tissue culture, immunology, molecular biology, microbiology, cell biology, and recombinant DNA, which are within the skill of the art. See, for example, Sambrook and Russelleds, (2001) Molecular Cloning: A Laboratory Manual, 3 rd edition; the seriesAusubel et al.eds. (2007) Current Protocols in Molecular Biology; the seriesMethods in Enzymology (Academic Press, Inc., NY); MacPherson et al. (1991) PCR 1: A Practical Approach (IRL Press at Oxford University Press); MacPherson et al. (1995) PCR 2: A Practical Approach; Harlow and Lane eds. (1999) Antibodies, A Laboratory Manual;

[0076] Freshney(2005)Culture of Animal Cells:A Manual of Basic Technique,5 thedition; Gait ed. (1984) Oligonucleotide Synthesis; USPat. No. 4,683,195; Hamesand Higgins eds. (1984) Nucleic Acid Hybridization; Anderson (1999) Nucleic AcidHybridization; Hames and Higgins eds. (1984) Transcription and Translation; Immobilized Cells and Enzymes (IRL) Press (1986)); Perbal (1984) A Practical Guide to Molecular Cloning; Miller and Calos eds, (1987) Gene Transfer Vectors for Mammalian Cells (Cold Spring Harbor Laboratory);

[0077] Makrides ed. (2003) Gene Transfer and Expression in Mammalian Cells; Mayer and Walker eds. (1987) Immunochemical Methods in Cell and Molecular Biology (Academic Press, London); and Herzenberg et al. eds (1996) Weir's Handbook of Experimental Immunology.

[0078] All numerical designations, such as pH values, temperatures, times, concentrations, and molecular weights, including ranges, are approximate and vary (+) or (-) in increments of 1.0 or 0.1, as appropriate, or alternatively vary by + / - 15%, or 10%, or 5%, or 2%. It should be understood that all numerical designations are preceded by the term "about," although not always explicitly stated. It should also be understood that the reagents described herein are exemplary only and that equivalents thereof are known in the art.

[0079] As used in the specification and claims, the singular includes plural referents unless the context clearly dictates otherwise. For example, the term "polypeptide" includes a plurality of polypeptides, including mixtures thereof.

[0080] As used herein, the term "comprising" is intended to indicate that compositions and methods include the recited elements, but do not exclude other elements. When used to define compositions and methods, "consisting essentially of" means excluding other elements that have any essential significance to the combination for the intended use. Thus, a composition consisting essentially of the elements defined herein does not exclude trace contaminants and pharmaceutically acceptable carriers, such as phosphate-buffered saline, preservatives, etc., from separation and purification methods. "Consisting of" means excluding other ingredients more than trace elements and the essential method steps for administering the compositions disclosed herein. Embodiments defined by each of these transition terms are within the scope of this disclosure.

[0081] "Biofilm" refers to an organized community of microorganisms (which sometimes attach to surfaces that may be organic or inorganic structures) and polymers (such as DNA) that they secrete, release, and / or become available in the extracellular environment due to bacterial lysis. Biofilms are highly resistant to microorganisms and antimicrobial agents. They live on gum tissue, teeth, and restorations, causing caries and periodontal disease, also known as periodontal plaque. They can also cause chronic middle ear infections. Biofilms can also form on the surfaces of dental implants, stents, catheter lines, and contact lenses. They grow on pacemakers, heart valve replacements, artificial joints, and other surgical implants. The Centers for Disease Control estimates that more than 65% of hospital-acquired infections are caused by biofilms. They can cause chronic vaginal infections and life-threatening systemic infections in people with compromised immune systems. Biofilms are also associated with many diseases. For example, cystic fibrosis patients suffer from Pseudomonas infections, which often develop antibiotic-resistant biofilms. In one embodiment, the biofilm comprises DNABII polypeptides or proteins. In a further embodiment, the biofilm comprises IHF and / or HU. In yet another embodiment, the biofilm comprises IHFAs and / or IHFBs.

[0082] The term "disruption" is intended to reduce the formation of the DNA / protein matrix that is a component of a microbial biofilm. In certain embodiments, disrupting a biofilm refers to dispersing the biofilm, releasing the microorganisms from the DNA / protein matrix of the biofilm, and optionally allowing host immune effectors and / or antibiotics to kill the microorganisms.

[0083] " DNABII polypeptide or protein " means to be made up of DNA binding domain and therefore have DNA binding protein or polypeptide of specificity or general affinity to microbial DNA.On the one hand, they are attached to the minor groove of DNA.The non-limiting example of DNABII protein is integration host factor (IHF) albumen and the histone-like protein (HU) from Escherichia coli strain U93.Other may comprise DPS (Genbank accession number: CAA49169), H-NS (Genbank accession number: CAA47740), Hfq (Genbank accession number: ACE63256), CbpA (Genbank accession number: BAA03950) and CbpB (Genbank accession number: NP03950). _ 418813).

[0084] " integration host factor " or " IHF " albumen is a kind of bacterial protein, is used for its DNA to be integrated in host bacteria by phage.They also combine extracellular microbial DNA.The gene of encoding IHF protein subunit in Escherichia coli is himA (Genbank accession number: POA6X7.1) and himD (POA6Y1.1) gene.The homologue of these genes is present in other organisms.In certain embodiments, term " IHF " refers to one or both of two IHF subunits: integration host factor subunit α (IHFA or IhfA) and integration host factor subunit β (IHFB or IhfB).

[0085] "HU" or "histone-like protein from Escherichia coli strain U93" refers to a class of heterodimeric proteins generally associated with E. coli. HU proteins are known to bind to DNA junctions. Related proteins have been isolated from other microorganisms. The complete amino acid sequence of E. coli HU was reported by Laine et al. (Laine et al. (1980) Eur. J. Biochem 103(3) 447-481). Antibodies to the HU protein are commercially available from Abeam. The genes encoding the HU protein subunits in E. coli are hupA and hupB, corresponding to SEQ ID NOs: 29 and 30, respectively. Homologs of these genes exist in other organisms, and peptides corresponding to these genes from other organisms can be found in WO

[0086] 2011 / 123396 can be found in Table 10.

[0087] The term "surface antigen" or "surface protein" refers to a protein or peptide on the surface of a cell, such as a bacterial cell. Examples of outer membrane proteins are, for example, OMP P5 (Genbank Accession No.: YP-004139079.1), OMP P2 (Genbank Accession No.: ZZX87199.1), and OMP P26 (Genbank Accession No.: YP-665091.1), while examples of surface antigens are rsPilA or recombinant soluble PilA (Genbank Accession No.: EFU96734.1) and type IV fimbriae protein (Genbank Accession No.: Yp-003864351.1).

[0088] The term "Haemophilus influenzae" refers to a pathogen that can cause many different infections, such as ear infections, eye infections, and sinusitis. Many different strains of Haemophilus influenzae have been isolated and possess the ihfA, ihfB, and hupA genes or proteins. Some non-limiting examples of different Haemophilus influenzae strains include Rd KW20, 86-028NP, R2866, PittGG, PittEE, R2846, and 2019.

[0089] "Microbial DNA" refers to single-stranded or double-stranded DNA from microorganisms that are incorporated into a biofilm.

[0090] "Inhibiting, preventing or disrupting" a biofilm means prophylactically or therapeutically reducing the structure of the biofilm.

[0091] "Bent polynucleotide" means a double-stranded polynucleotide comprising a small loop on one strand that does not pair with the other strand. In some embodiments, the loop is about 1 base to about 20 bases long, or alternatively about 2 bases to about 15 bases long, or alternatively about 3 bases to about 12 bases long, or alternatively about 4 bases to about 10 bases long, or alternatively has about 4, 5, or 6, or 7, or 8, or 9, or 10 bases.

[0092] " in conjunction with the polypeptide of competition of DNABII, for example, in conjunction with DNA, compete with IHF " refer to and compete with DNABII (for example IHF) in conjunction with the DNA structure of bending or distortion but not with DNA to form biomembrane protein or peptide.Example includes but not limited to the fragment of IHF, it comprises one or more DNA binding structural domains of IHF, or its biological equivalent.

[0093] The " object " of diagnosis or treatment is a cell or animal, such as a mammal or a human. The non-human animals receiving diagnosis or treatment are those infected animals or animal models, such as monkeys, murines (such as rats, mice, chinchillas), canines (such as dogs), lagomorphs (such as rabbits), livestock, competitive animals and pets. The terms " object ", " host ", " individual " and " patient " are used interchangeably herein to refer to animals, typically mammals. The non-limiting examples of mammals include humans, non-human primates (such as apes, gibbons, chimpanzees, orangutans, monkeys, macaques, etc.), domestic animals (such as dogs and cats), farm animals (such as horses, cattle, goats, sheep, pigs) and experimental animals (such as mice, rats, rabbits, guinea pigs). In some embodiments, mammals are humans. Mammals can be of any age or in any developmental stage (such as adults, teenagers, children, infants or mammals in the womb). Mammals can be male or female. In some embodiments, subjects are humans.

[0094] The terms "protein," "peptide," and "polypeptide" are used interchangeably and in their broadest sense refer to a complex of two or more subunit amino acids, amino acid analogs, or peptidomimetics. The subunits may be linked by peptide bonds. In another embodiment, the subunits may be linked by other bonds, such as esters, ethers, and the like. A protein or peptide must contain at least two amino acids, and there is no limit on the maximum number of amino acids that can constitute a protein or peptide sequence. As used herein, the term "amino acid" refers to natural and / or unnatural or synthetic amino acids, including glycine and its D and L optical isomers, amino acid analogs, and peptidomimetics.

[0095] "C-terminal polypeptide" means at least the 10, or at least 15, or at least 20, or at least 25 C-terminal amino acids of a polypeptide or half a polypeptide. On the other hand, for a polypeptide containing 90 amino acids, the C-terminal polypeptide will include amino acids 46 to 90. In one aspect, the term means the C-terminal 20 amino acids starting from the carboxyl terminus.

[0096] The "head segment" of the DNABII polypeptide refers to the two arms that form the protein, for example, IHFalpha and IHFbeta (see Figure 1 Non-limiting examples of this class include IhfA, A head fragment: NFELRDKSSRPGRNPKTGDVV, SEQ ID NO: 31, and IhfB, B head fragment: SLHHRQPRLGRNPKTGDSVNL, SEQ ID NO: 32.

[0097] The "tail segment" of the DNABII polypeptide refers to the region of the protein that is exposed to the bulk medium and is not masked by DNA or other polypeptides.

[0098] Immunodominant antigens are regions of proteins that are recognized and bound by antibodies with high affinity.

[0099] An immunoprotective antigen is a region of a protein that is recognized and bound by antibodies with high affinity, thereby interfering with protein function; antibodies generated against immunoprotective antigens are characterized by enhanced or optimal efficacy against the target indication due to interference with protein function—in this case, improved ability to clear biofilms.

[0100] The terms "polynucleotide" and "oligonucleotide" are used interchangeably and refer to a polymeric form of nucleotides of any length, whether deoxyribonucleotides or ribonucleotides or their analogs. Polynucleotides can have any three-dimensional structure and can perform any known or unknown function. The following are non-limiting examples of polynucleotides: genes or gene fragments (e.g., probes, primers, EST or SAGE tags), exons, introns, messenger RNA (mRNA), transfer RNA, ribosomal RNA, RNAi, ribozymes, cDNA, recombinant polynucleotides, branched polynucleotides, plasmids, vectors, isolated DNA of any sequence, isolated RNA of any sequence, nucleic acid probes and primers. Polynucleotides can include modified nucleotides, such as methylated nucleotides and nucleotide analogs. If present, modifications to the nucleotide structure can be imparted before or after polynucleotide assembly. The nucleotide sequence can be interrupted by non-nucleotide components. Polynucleotides can be further modified after polymerization, for example, by conjugating with a labeling component. The term also refers to double-stranded and single-stranded molecules. Unless otherwise stated or required, any embodiment of a polynucleotide disclosed herein encompasses both a double-stranded form and each of the two complementary single-stranded forms known or predicted to comprise the double-stranded form.

[0101] A polynucleotide consists of a specific sequence of four nucleotide bases: adenine (A); cytosine (C); guanine (G); and thymine (T). When the polynucleotide is RNA, uracil (U) replaces thymine. Thus, the term "polynucleotide sequence" is an alphabetic representation of a polynucleotide molecule. This alphabetic representation can be entered into a database on a computer with a central processing unit and used in bioinformatics applications such as functional genomics and homology searches.

[0102] As used herein, the terms "isolated" or "recombinant" with respect to nucleic acids, such as DNA or RNA, refer to molecules that are separated from other DNA or RNA present in the natural sources of macromolecules and polypeptides, respectively. The term "isolated or recombinant nucleic acid" is intended to include nucleic acid fragments that do not exist naturally as fragments and are not found in nature. The term "isolated" is also used herein to refer to polynucleotides, polypeptides, and proteins separated from other cellular proteins, and is intended to include purified and recombinant polypeptides. In other embodiments, the term "isolated or recombinant" means separated from cells and other components, wherein cells, tissues, polynucleotides, peptides, polypeptides, proteins, antibodies, or fragments thereof are typically naturally associated with each other. For example, an isolated cell is a cell separated from a tissue or cell with a different phenotype or genotype. An isolated polynucleotide is separated from the 3' and 5' consecutive nucleotides to which it is normally associated in its natural or natural environment (e.g., on a chromosome). As will be apparent to those skilled in the art, non-naturally occurring polynucleotides, peptides, polypeptides, proteins, antibodies, or fragments thereof do not need to be "isolated" to distinguish them from their naturally occurring counterparts.

[0103] In the absence of explicit narration and unless otherwise indicated, it can be inferred that when the present disclosure relates to polypeptides, proteins, polynucleotides or antibodies, their equivalents or bioequivalents are included within the scope of the present disclosure. As used herein, the term "bioequivalent thereof" is intended to be synonymous with "equivalent thereof" when referring to a reference protein, antibody, fragment, polypeptide or nucleic acid, meaning those equivalents having minimal homology while still maintaining desired structure or functionality. Unless specifically mentioned herein, it is contemplated that any polynucleotide, polypeptide or protein mentioned herein also includes equivalents thereof. On the one hand, equivalent polynucleotides are polynucleotides that hybridize under stringent conditions with the polynucleotides or complements of the polynucleotides used for the method as described herein. In another aspect, equivalent antibodies or antigen-binding polypeptides mean binding with an affinity of at least 70%, or at least 75%, or at least 80%, or at least 85%, or at least 90%, or at least 95% or higher relative to a reference antibody or antigen-binding fragment. In another aspect, equivalents thereof compete with antibodies or antigen-binding fragments for binding to their antigens under competitive ELISA assays. On the other hand, an equivalent means at least about 80% homology or identity, or at least about 85%, or at least about 90%, or at least about 95%, or 98% homology or identity, and exhibits substantially the same biological activity as the reference protein, polypeptide or nucleic acid. Examples of biologically equivalent polypeptides are provided in Table 9 of WO 2011 / 123396, which identifies conservative amino acid substitutions to the disclosed amino acid sequences.

[0104] A polynucleotide or polynucleotide region (or polypeptide or polypeptide region) that has a certain percentage (e.g., 80%, 85%, 90% or 95%) of "sequence identity" to another sequence means that, when aligned, the number of bases (or amino acids) in that percentage is the same when the two sequences are compared. Alignments and percent homology or sequence identity can be determined using software programs known in the art, such as those described in Current Protocols in Molecular Biology (Ausubel et al., eds. 1987) Supplement 30, section 7.7.18, Table 7.7.1. In certain embodiments, the alignment is performed using default parameters. A non-limiting exemplary alignment program is BLAST, using default parameters. Specifically, exemplary programs include BLASTN and BLASTP, using the following default parameters: Genetic code = standard; filter = none; strand = both; cutoff = 60; expect = 10;

[0105] Matrix=BLOSUM62; Descriptions=50sequences; sort by=HIGH SCORE; Databases=non-redundant,GenBank+EMBL+DDBJ+PDB+GenBank CDS translations+SwissProtein+

[0106] SPupdate+PIR. Detailed information on these programs can be found at the following Internet addresses:

[0107] ncbi.nlm.nih.gov / cgi-bin / BLAST. Sequence identities and percent identities were determined by merging them into clustalW (website: align.genome.jp, last accessed March 7, 2011).

[0108] "Homology" or "identity" or "similarity" refers to the sequence similarity between two peptides or between two nucleic acid molecules. Homology can be determined by comparing positions in each sequence, which can be aligned for the purpose of comparison. When a position in the compared sequences is occupied by the same base or amino acid, then the molecules are homologous at that position. The degree of homology between sequences is a function of the number of matching or homologous positions shared by the sequences. An "unrelated" or "nonhomologous" sequence has less than 40% identity, or less than 25% identity, to one of the sequences of the present disclosure.

[0109] "Homology" or "identity" or "similarity" may also refer to two nucleic acid molecules that hybridize under stringent conditions.

[0110] "Hybridization" refers to the reaction of one or more polynucleotides to form a complex that is stabilized by hydrogen bonding between the bases of the nucleotide residues. Hydrogen bonding can occur by Watson-Crick base pairing, Hoogstein binding, or any other sequence-specific manner. The complex can comprise two chains forming a duplex structure, three or more chains forming a multi-chain complex, a single self-hybridizing chain, or any combination of these. A hybridization reaction can constitute a step in a broader process, such as the start of a PCR reaction, or the enzymatic cleavage of a polynucleotide by a ribozyme.

[0111] Examples of stringent hybridization conditions include: an incubation temperature of about 25°C to about 37°C; a hybridization buffer concentration of about 6×SSC to about 10×SSC; a formamide concentration of about 0% to about 25%; and a wash solution of about 4×SSC to about 8×SSC. Examples of moderate hybridization conditions include: an incubation temperature of about 40°C to about 50°C; a buffer concentration of about 9×SSC to about 2×SSC; a formamide concentration of about 30% to about 50%; and a wash solution of about 5×SSC to about 2×SSC. Examples of high stringency conditions include: an incubation temperature of about 55°C to about 68°C; a buffer concentration of about 1×SSC to about 0.1×SSC; a formamide concentration of about 55% to about 75%; and a wash solution of about 1×SSC, 0.1×SSC, or deionized water. Typically, the hybridization incubation time is 5 minutes to 24 hours, with 1, 2, or more wash steps, and the wash incubation time is about 1, 2, or 15 minutes. SSC is a 0.15 M NaCl and 15 mM citrate buffer. It will be appreciated that SSC equivalents using other buffer systems may be employed.

[0112] As used herein, "expression" refers to the process by which a polynucleotide is transcribed into mRNA and / or the process by which the transcribed mRNA is subsequently translated into a peptide, polypeptide, or protein. If the polynucleotide is derived from genomic DNA, expression may include splicing of the mRNA in eukaryotic cells.

[0113] The term "encoding" when applied to a polynucleotide refers to a polynucleotide that, in its native state or when manipulated by methods well known to those skilled in the art, can be transcribed and / or translated to produce mRNA for a polypeptide and / or fragment thereof. The antisense strand is the complementary sequence of such a nucleic acid, from which the coding sequence can be deduced.

[0114] As used herein, the term "treat" is used herein to mean obtaining a desired pharmacological and / or physiological effect. The effect may be preventive in terms of completely or partially preventing a condition or its signs or symptoms, and / or therapeutic in terms of partially or completely curing a condition and / or adverse effects attributable to the condition. As used herein, "treating" a disease in a subject may also refer to (1) preventing symptoms or disease from occurring in a subject susceptible to or not yet exhibiting symptoms of the disease; (2) inhibiting the disease or arresting its development; or (3) ameliorating or causing regression of the disease or disease symptoms. As understood in the art, "treatment" is a method for obtaining a beneficial or desired result (including a clinical result). For the purposes of the present technology, a beneficial or desired result may include, but is not limited to, alleviation or improvement of one or more symptoms, alleviation of the extent of a condition (including a disease), stabilization (i.e., not worsening) of a condition (including a disease), delay or slowing of a condition (including a disease), progression, improvement or alleviation of a condition (including a disease), condition, and remission (whether partial or complete), whether detectable or undetectable. In one aspect, treatment does not include prevention.

[0115] Prevention means preventing a disease or effect in vitro or in vivo in a system or subject susceptible to the disease or effect. An example of this is preventing the formation of a biofilm in a system infected with microorganisms known to produce biofilms.

[0116] "Composition" is intended to mean a combination of an active agent and another compound or an inert (e.g., a detectable agent or marker) or active ingredient, such as an adjuvant, diluent, binder, stabilizer, buffer, salt, lipophilic solvent, preservative, adjuvant, etc., and includes a pharmaceutically acceptable carrier. Carriers also include pharmaceutical excipients and additives proteins, peptides, amino acids, lipids and carbohydrates (e.g., sugars, including monosaccharides, di-oligosaccharides, tri-oligosaccharides, tetra-oligosaccharides and oligosaccharides; Derivatized sugars, such as sugar alcohols, aldonic acids, esterified sugars, etc.; and polysaccharides or sugar polymers), which may be present alone or in combination, alone or in combination, accounting for 1-99.99% by weight or volume. Exemplary protein excipients include serum albumin, such as human serum albumin (HSA), recombinant human albumin (rHA), gelatin, casein, etc. Representative amino acid / antibody components that may also play a role in buffering capacity include alanine, arginine, glycine, arginine, betaine, histidine, glutamic acid, aspartic acid, cysteine, lysine, leucine, isoleucine, valine, methionine, phenylalanine, aspartame, etc. Carbohydrate excipients are also included within the scope of the present technology, examples of which include, but are not limited to, monosaccharides such as fructose, maltose, galactose, glucose, D-mannose, sorbose, etc.; disaccharides such as lactose, sucrose, trehalose, cellobiose, etc.; polysaccharides such as raffinose, melezitose, maltodextrin, dextran, starch, etc.; and sugar alcohols such as mannitol, xylitol, maltitol, lactitol, xylitol, sorbitol (glucitol), and inositol.

[0117] A "pharmaceutical composition" is intended to include an active agent in combination with an inert or active carrier, making the composition suitable for diagnostic or therapeutic use in vitro, in vivo or ex vivo.

[0118] "Pharmaceutically acceptable carrier" refers to any diluent, excipient, or carrier that can be used in the compositions disclosed herein. Pharmaceutically acceptable carriers include ion exchangers, aluminum oxide, aluminum stearate, lecithin, serum proteins such as human serum albumin, buffer substances such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts, or electrolytes, such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silicon dioxide, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based substances, polyethylene glycol, sodium carboxymethyl cellulose, polyacrylates, waxes, polyethylene-polyoxypropylene-block polymers, polyethylene glycol, and lanolin. Suitable pharmaceutical carriers are described in Remington's Pharmaceutical Sciences, a standard reference text in this field, Mack Publishing Company. They can be selected based on the intended form of administration, i.e., oral tablets, capsules, elixirs, syrups, etc., and are consistent with conventional pharmaceutical practice.

[0119] The compositions used according to the present disclosure can be packaged in dosage unit form for the purpose of administration and uniformity of dosage. The term "unit dose" or "dosage" refers to a physically discrete unit applicable to an object, each unit containing a predetermined amount of compositions, which is calculated based on the desired reaction to be produced in accordance with the administration (i.e., appropriate approach and regimen). Depending on the number of treatments and the unit dose, the dosage depends on the desired result and / or protection. The precise amount of the compositions also depends on the practitioner's judgment and is unique to each individual. Factors affecting dosage include the physical and clinical state of the object, route of administration, intended therapeutic target (alleviation of symptoms vs. cure) and effectiveness, stability and toxicity of the specific compositions. When formulated, the solution is administered in a manner compatible with the dosage formulation and in an amount effective for treatment or prevention. Preparations are easily administered in a variety of dosage forms, such as injectable solution types described herein.

[0120] As disclosed herein, "biologically active agent" or active agent means one or more isolated or recombinant polypeptides, isolated or recombinant polynucleotides, vectors, isolated host cells, or antibodies, as well as compositions comprising one or more of these.

[0121] "Administration" can be carried out continuously or intermittently in the form of a single dose throughout the treatment process. Methods for determining the most effective mode of administration and dosage are known to those skilled in the art and will vary with the composition used for treatment, the purpose of treatment, the target cell being treated, and the subject being treated. Single or multiple administrations can be performed, and the dosage level and pattern are selected by the treating physician. Suitable dosage formulations and methods of administration are known in the art. The route of administration can also be determined, and methods for determining the most effective route of administration are known to those skilled in the art and will vary with the composition used for treatment, the purpose of treatment, the health condition or stage of disease, the subject being treated, and the target cell or tissue being treated. Non-limiting examples of routes of administration include oral administration, nasal administration, injection, and topical application.

[0122] The agents of the present disclosure can be administered for treatment by any suitable route of administration. It should also be understood that the optimal route will vary with the condition and age of the recipient and the disease being treated.

[0123] As used herein, the term "contacting" refers to the direct or indirect binding or interaction between two or more molecules. A specific example of a direct interaction is binding. A specific example of an indirect interaction is one entity acting on an intermediary molecule, which in turn acts on a second reference entity. As used herein, contacting includes contacting in solution, in a solid phase, in vitro, ex vivo, in a cell, and in vivo. In vivo contacting can also be referred to as administration or dosing.

[0124] The term "effective amount" refers to an amount sufficient to achieve the desired effect. In the case of therapeutic or preventive applications, the effective amount will depend on the type and severity of the condition in question and the characteristics of the individual subject, such as general health, age, sex, weight, and tolerance to the pharmaceutical composition. In the case of immunogenic compositions, in some embodiments, the effective amount is an amount sufficient to cause a protective response against the pathogen. In other embodiments, the effective amount of the immunogenic composition is an amount sufficient to cause the production of antibodies against the antigen. In some embodiments, the effective amount is the amount required to confer passive immunity to a subject in need. With regard to immunogenic compositions, in some embodiments, in addition to the factors mentioned above, the effective amount will depend on the intended use, the degree of immunogenicity of the specific antigenic compound, and the health / reactivity of the subject's immune system. Those skilled in the art will be able to determine the appropriate amount based on these and other factors.

[0125] In the case of in vitro applications, in some embodiments, the effective amount will depend on the size and nature of the application. It also depends on the nature and sensitivity of the in vitro target and the method used. Those skilled in the art will be able to determine the effective amount based on these and other considerations. Depending on the embodiment, the effective amount may include one or more administrations of the composition.

[0126] The term "contacting" refers to the direct or indirect binding or interaction between two or more molecules. A specific example of a direct interaction is binding. A specific example of an indirect interaction is one entity acting on an intermediary molecule, which in turn acts on a second reference entity. As used herein, contacting includes contacting in solution, in a solid phase, in vitro, ex vivo, in a cell, and in vivo. In vivo contacting can also be referred to as administration or dosing.

[0127] The term "conjugate moiety" refers to a moiety that can be added to an isolated chimeric polypeptide by forming a covalent bond with a residue of the chimeric polypeptide. The moiety can be directly bound to the residue of the chimeric polypeptide or can form a covalent bond with a linker that in turn forms a covalent bond with a residue of the chimeric polypeptide.

[0128] "Peptide conjugate" refers to the association of one or more polypeptides with another chemical or biological compound through covalent or non-covalent bonding. In a non-limiting example, "conjugation" of a polypeptide to a compound results in increased stability or efficacy of the polypeptide for its intended purpose. In one embodiment, the peptide is conjugated to a carrier, wherein the carrier is a liposome, micelle, or pharmaceutically acceptable polymer.

[0129] "Liposomes" are microscopic vesicles composed of concentric lipid bilayers. Structurally, liposomes vary in size and shape from long tubes to spheres, and in dimensions from a few hundred angstroms to a fraction of a millimeter. The lipids that form the vesicles are selected to achieve a particular degree of fluidity or rigidity in the final complex, thereby providing the lipid components of the outer layer. These are neutral (cholesterol) or bipolar, and include phospholipids such as phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and sphingomyelin (SM), as well as other types of bipolar lipids, including but not limited to dioleoylphosphatidylethanolamine (DOPE), with hydrocarbon chain lengths ranging from 14-22, saturated or having one or more C=C double bonds. Examples of lipids that can produce stable liposomes, alone or in combination with other lipid components, are phospholipids, such as hydrogenated soybean phosphatidylcholine (HSPC), phosphatidylcholine, phosphatidylethanolamine, lysolecithin, lysolecithin, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, cephalin, cardiolipin, phosphatidic acid, cerebrosides, distearoylphosphatidylethanolamine (DSPE), dioleoylphosphatidylcholine (DOPC), dipalmitoylphosphatidylcholine (DPPC), palmitoylphosphatidylcholine (POPC), palmitoyloleoylphosphatidylethanolamine (POPE), and dioleoylphosphatidylethanolamine 4-(N-maleimido-triethyl)cyclohexane-1-carboxylate (DOPE-mal). Other non-phosphorus-containing lipids that can be incorporated into liposomes include stearylamine, dodecylamine, hexadecylamine, isopropyl myristate, triethanolamine-lauryl sulfate, alkyl aryl sulfate, acetyl palmitate, glyceryl ricinoleate, hexadecyl stearate, amphoteric acrylic polymers, polyethoxylated fatty acid amides and above-mentioned cationic lipids (DDAB, DODAC, DMRIE, DMTAP, DOGS, DOTAP (DOTMA), DOSPA, DPTAP, DSTAP, DC-Chol). Negatively charged lipids include phosphatidic acid (PA), dipalmitoylphosphatidylglycerol (DPPG), disulfide phosphatidylglycerol and (DOPG) and hexacosyl phosphate that can form vesicles. Generally, liposomes can be divided into three categories according to the properties of their overall size and lamellar structure. According to the December 1977 New York Academy of Sciences meeting "Liposomes and Their Use in Biology and Medicine", the three classifications are multilamellar vesicles (MLV), small unilamellar vesicles (SUV) and large unilamellar vesicles (LUV). Biologically active agents can be encapsulated therein for administration according to the methods described herein.

[0130] "Micelles" are aggregates of surfactant molecules dispersed in a liquid colloid. Typical micelles in aqueous solution form aggregates in which the hydrophilic "head" region is in contact with the surrounding solvent, isolating the hydrophobic tail region in the center of the micelle. This type of micelle is called a normal micelle (oil-in-water micelle). Reverse micelles have a head in the center and a tail extending outward (water-in-oil micelle). Micelles can be used to link polynucleotides, polypeptides, antibodies, or compositions described herein to facilitate efficient delivery to target cells or tissues.

[0131] The phrase "pharmaceutically acceptable polymer" refers to a group of compounds that can be conjugated to one or more polypeptides described herein. It is expected that conjugation of polymers to polypeptides can extend the half-life of the polypeptides in vivo and in vitro. Non-limiting examples include polyethylene glycol, polyvinyl pyrrolidone, polyvinyl alcohol, cellulose derivatives, polyacrylates, polymethacrylates, sugars, polyols, and mixtures thereof. Bioactive agents can be conjugated to pharmaceutically acceptable polymers for administration according to the methods described herein.

[0132] A "gene delivery vector" is defined as any molecule that can carry an inserted polynucleotide into a host cell. Examples of gene delivery vectors are liposomes, micelles, biocompatible polymers, including natural and synthetic polymers; lipoproteins; polypeptides; polysaccharides; lipopolysaccharides; artificial viral envelopes; metal particles; and bacteria or viruses, such as baculoviruses, adenoviruses, and retroviruses, phages, cosmids, plasmids, fungal vectors, and other recombinant vectors commonly used in the art that have been described for expression in a variety of eukaryotic and prokaryotic hosts and can be used for gene therapy as well as simple protein expression.

[0133] The polynucleotides disclosed herein can be delivered to cells or tissues or objects using gene delivery vectors. As used herein, "gene delivery," "gene transfer," "transduction," etc. refer to the terminology of exogenous polynucleotides (sometimes referred to as "transgenics") being introduced into host cells, regardless of the method of introduction. Such methods include a variety of well-known technologies, such as vector-mediated gene transfer (by, for example, viral infection / transfection, or various other protein-based or lipid-based gene delivery complexes) and the technology (such as electroporation, "gene gun" delivery, and various other technologies for introducing polynucleotides) that promotes the delivery of "naked" polynucleotides. The polynucleotides introduced can be stably or transiently maintained in the host cell. Stable maintenance generally requires that the polynucleotides introduced include a replication origin compatible with the host cell or be integrated into the replicon of the host cell, such as an extrachromosomal replicon (such as a plasmid) or a nuclear or mitochondrial chromosome. As known in the art and described herein, many vectors are known to be able to mediate the transfer of genes to mammalian cells.

[0134] As used herein, the term "cDNA" refers to extracellular DNA found as a component of pathogenic biofilms.

[0135] A "plasmid" is an extrachromosomal DNA molecule that is separate from chromosomal DNA and capable of replicating independently of it. In many cases, it is circular and double-stranded. Plasmids provide a mechanism for horizontal gene transfer within a microbial population and often provide a selective advantage under given environmental conditions. Plasmids may carry genes that confer resistance to naturally occurring antibiotics in competitive environments, or they may produce proteins that act as toxins under similar circumstances.

[0136] A "plasmid" used in genetic engineering is called a "plasmid vector." Many plasmids are commercially available for this purpose. The gene to be replicated is inserted into multiple copies of a plasmid that contains the gene that makes the cell resistant to a specific antibiotic and a multiple cloning site (MCS, or polylinker), where the multiple cloning site is a short region containing several common restriction sites that allows DNA fragments to be easily inserted at this location. Another major use of plasmids is to make large quantities of proteins. In this case, researchers grow bacteria that contain a plasmid with the gene of interest. Just as the bacterium produces proteins to confer antibiotic resistance, it can also be induced to produce large quantities of protein from the inserted gene. This is a cheap and simple way to mass-produce a gene or encoded protein.

[0137] "Yeast artificial chromosome" or "YAC" refers to a vector used to clone large DNA fragments (greater than 100kb and up to 3000kb). It is an artificially constructed chromosome that contains the telomere, centromere and replication origin sequences required for replication and maintenance in yeast cells. It is constructed using an initial circular plasmid, which is linearized using restriction endonucleases, and then DNA ligase can add the sequence or gene of interest within the linear molecule through the use of sticky ends. Yeast expression vectors such as YAC, YIp (yeast integrating plasmid) and YEp (yeast episomal plasmid) are very useful because yeast is itself a eukaryotic cell, so eukaryotic protein products with post-translational modifications can be obtained, but YACs have been found to be more unstable than BACs and produce chimeric effects.

[0138] "Viral vector" is defined as a recombinantly produced virus or viral particle containing a polynucleotide to be delivered into a host cell in vivo, ex vivo or in vitro. Examples of viral vectors include retroviral vectors, adenoviral vectors, adeno-associated viral vectors, alphaviral vectors, and the like. Vectors based on the infectious tobacco mosaic virus (TMV) can be used to produce proteins, and it has been reported that Griffithsin can be expressed in tobacco leaves (O'Keefe et al. (2009) Proc. Nat. Acad. Sci. USA 106 (15): 6099-6104). Alphaviral vectors, such as vectors based on Semliki Forest virus and vectors based on Sindbis virus, have also been developed for gene therapy and immunotherapy. See Schlesinger &

[0139] Dubensky (1999) Curr. Opin. Biotechnol. 5:434-439 and Ying et al. (1999) Nat. Med.

[0140] 5(7):823-827. In aspects where gene transfer is mediated by a retroviral vector, the vector construct refers to a polynucleotide comprising the retroviral genome or a portion thereof and the therapeutic gene.

[0141] As used herein, "retroviral-mediated gene transfer" or "retroviral transduction" have the same meaning and refer to the process of stably transferring a gene or nucleic acid sequence into a host cell by virtue of the virus entering the cell and integrating its genome into the host cell genome. Viruses can enter host cells through their normal infection mechanisms or by being modified to bind to different host cell surface receptors or ligands. As used herein, a retroviral vector refers to a viral particle capable of introducing exogenous nucleic acid into a cell through a viral or virus-like entry mechanism.

[0142] Retroviruses carry their genetic information in the form of RNA; however, once the virus infects a cell, the RNA is reverse-transcribed into DNA and integrated into the infected cell's genomic DNA. This integrated DNA form is called a provirus.

[0143] In aspects where gene transfer is mediated by a DNA viral vector, such as adenovirus (Ad) or adeno-associated virus (AAV), a vector construct refers to a polynucleotide comprising the viral genome or portion thereof and a transgene. Adenovirus (Ad) is a relatively well-characterized homologous group of viruses that includes more than 50 serotypes. See, for example, PCT International Application Publication No. WO 95 / 27071. Ad does not need to be integrated into the host cell genome. Recombinant Ad-derived vectors have also been constructed, particularly those that reduce the likelihood of recombination and production of wild-type virus. See PCT International Application Publication Nos. WO 95 / 00655 and WO 95 / 11984. Wild-type AAV has high infectivity and specificity for integration into the host cell genome. See Hermonat & Muzyczka (1984) Proc. Natl. Acad. Sci. USA 81:6466-6470 and Lebkowski et al. (1988) Mol. Cell. Biol. 8:3988-3996.

[0144] The carrier that comprises promoter and the cloning site that is operably connected polynucleotide is well known in the art.This type of carrier can transcribe RNA in vitro or in vivo, and can be commercially available from sources such as Stratagene (La Jolla, CA) and PromegaBiotech (Madison, Wis.).In order to optimize expression and / or in vitro transcription, it may be necessary to remove, add or change the 5 ' and / or 3 ' non-translated portion of the clone to eliminate additional, potential inappropriate alternative translation initiation codon or other sequences that may interfere or reduce expression on transcription or translation level. Alternatively, a consensus ribosome bind site can be inserted immediately at the 5 ' place of the start codon to enhance expression.

[0145] Gene delivery vehicles also include DNA / liposome complexes, micelles, and targeted viral protein-DNA complexes. Liposomes further comprising targeting antibodies or fragments thereof can be used in the methods disclosed herein. In addition to delivering polynucleotides to cells or cell populations, proteins described herein can be directly introduced into cells or cell populations by non-limiting techniques such as protein transfection, or, other non-limiting techniques, culturing under conditions that enhance expression and / or promote activity of proteins disclosed herein.

[0146] As used herein, the terms "antibody" and "immunoglobulin" include complete antibodies and any antigen-binding fragments or single chains thereof. Thus, the term "antibody" includes any protein- or peptide-containing molecule that comprises at least a portion of an immunoglobulin molecule. The terms "antibody" and "immunoglobulin" also include immunoglobulins of any isotype, antibody fragments that retain specific binding to an antigen, including but not limited to Fab, Fab', F(ab)2, Fv, scFv, dsFv, Fd fragments, dAb, VH, VL, VhH, and V-NAR domains; minibodies, diabodies, trimers, tetrabodies, and kappa bodies; and multispecific antibody fragments formed from one or more isolated antibody fragments. Such examples include but are not limited to the complementarity determining regions (CDRs) of heavy or light chains or their ligand-binding portions, heavy or light chain variable regions (also referred to herein as variable regions), heavy or light chain constant regions (also referred to herein as constant regions), framework (FR) regions or any portion thereof, at least a portion of a binding protein, chimeric antibodies, humanized antibodies, single-chain antibodies, and fusion proteins comprising the antigen-binding portion of an antibody and a non-antibody protein. The variable region of the heavy chain of immunoglobulin molecule and light chain comprises the binding domain that interacts with antigen.The constant region of antibody (Ab) can mediate the combination of immunoglobulin and host tissue.For example, when using the term " anti- " before the protein name, for example anti-DNABII, anti-IHF, anti-HU, anti-OMP P5, refer to the monoclonal or polyclonal antibody in conjunction with specific protein and / or specific protein has avidity.For example, " anti-IHF " refers to the antibody with IHF protein bonded.Specific antibody may have avidity or combination with the protein beyond the protein to which it is directed.For example, anti-IHF, although produces at the IHF protein specificity, also may be combined with other proteins related because of sequence homology or structural homology.

[0147] Complementarity determining region (CDR) is a part of the variable region of the antibody or T cell receptor produced by B cells and T cells respectively, wherein these molecules are combined with their specific antigen (also referred to as epitope).In certain embodiments, the terms "variable region" and "variable domain" are used interchangeably, referring to the polypeptide of antibody light chain or heavy chain, whose amino acid residue sequence varies greatly from one antibody to another antibody, and determines the conformation of the binding site, which gives the antibody specificity to a particular antigen.In a further embodiment, the variable region is about 90 amino acids long to about 200 amino acids long, including but not limited to about 100 amino acids long, or alternatively about 110 amino acids long, or alternatively about 120 amino acids long, or alternatively about 130 amino acids long, or alternatively about 140 amino acids long, or alternatively about 150 amino acids long, or alternatively about 160 amino acids long, or alternatively about 170 amino acids long, or alternatively about 180 amino acids long, or alternatively about 190 amino acids long. In certain embodiments, the variable region of an amino acid sequence as used herein refers to the first about 100 amino acids, or about 110 amino acids, or about 120 amino acids, or about 130 amino acids, or about 140 amino acids, or about 150 amino acids (including or excluding the signal peptide, if applicable) of the amino acid sequence are the variable region.

[0148] A group of CDRs constitutes a paratope, also known as an antigen binding site, which is the part of an antibody that recognizes and binds to an antigen. There are three non-contiguously arranged CDRs (CDR1, CDR2, and CDR3) optionally from the amino terminus to the carboxyl terminus on the variable region amino acid sequence of an antigen receptor, such as a heavy chain or a light chain. As used herein, CDRn refers to a CDRn in an immunoglobulin chain or derived from an immunoglobulin chain, wherein the number n is selected from 1-3. In one embodiment, CDRLn refers to a CDRn in a light chain or derived from a light chain, wherein the number n is selected from 1-3; and CDRHn refers to a CDRHn in a heavy chain or derived from a heavy chain, wherein the number n is selected from 1-3. In certain embodiments, a framework region (FR) refers to a portion of a variable region that is not a CDR. In certain embodiments, FRn refers to a FR in a heavy chain or a light chain or derived from a heavy chain or a light chain, and wherein the number n is selected from 1-4. In certain embodiments, the variable region comprises, consists essentially of, or further consists of (optionally in the order provided, and further optionally from amino-terminus to carboxyl-terminus): FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4.

[0149] The variable regions and / or CDRs of antibodies or fragments thereof can be determined by one skilled in the art, for example, using publicly or commercially available tools. Non-limiting examples of such tools include IgBlast (available at

[0150] www.ncbi.nlm.nih.gov / igblast / ), Scaligner (available from drugdesigntech at

[0151] www.scaligner.com / ), IMGT rules and / or tools (see, e.g., www.imgt.org / IMGTScientificChart / Nomenclature / IMGT-FRCDRdefinition.html, also available at www.imgt.org / ), Chothia Canonical Assignment (available at

[0152] ), Antigen receptor Numbering And Receptor Calculation (ANARCI, available at opig.stats.ox.ac.uk / webapps / newsabdab / sabpred / anarci / ), the Kabat numbering method / scheme (e.g., Kabat, EA, et al., (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, US Department of Health and Human Services, NIH Publication No. 91-3242), or the Paratome web server (available at www.ofranlab.org / paratome / , see Vered Kunik, et al, Nucleic Acids Research, Volume 40, Issue W1, 1 July 2012, Pages W521–W524).

[0153] Antibodies can be polyclonal, monoclonal, multispecific (eg, bispecific antibodies), and antibody fragments, so long as they exhibit the desired biological activity. Antibodies can be isolated from any suitable biological source, such as murine, rat, sheep, and dog.

[0154] As used herein, the term "polyclonal antibody" or "polyclonal antibody composition" refers to an antibody preparation derived from different B cell lines. They are a mixture of immunoglobulin molecules secreted against a specific antigen, each molecule recognizing a different epitope.

[0155] As used herein, "monoclonal antibody" refers to an antibody obtained from a substantially homogeneous antibody population. Monoclonal antibodies are highly specific because each monoclonal antibody is directed against a single determinant on the antigen. Antibodies can be detectably labeled, for example, with radioisotopes, enzymes that produce detectable products, fluorescent proteins, etc. The antibody can be further conjugated to other moieties, such as members of specific binding pairs, such as biotin (a member of the biotin-avidin specific binding pair), etc. The antibody can also be bound to a solid support, including but not limited to polystyrene plates or beads, etc.

[0156] Monoclonal antibodies can be produced using hybridoma technology or recombinant DNA methods known in the art. Hybridomas are cells formed in the laboratory by the fusion of antibody-producing lymphocytes and non-antibody-producing cancer cells (usually myeloma or lymphoma). Hybridomas proliferate and produce continuous samples of specific monoclonal antibodies. Alternative techniques for producing or selecting antibodies include exposing lymphocytes to the antigen of interest in vitro and screening antibody display libraries in cells, phage or similar systems.

[0157] As used herein, the term "human antibody" is intended to include antibodies having variable and constant regions derived from human germline immunoglobulin sequences. The human antibodies disclosed herein may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo). However, the term "human antibody" as used herein is not intended to include antibodies in which CDR sequences derived from the germline of another mammalian species, such as a mouse, have been grafted onto human framework sequences. Thus, as used herein, the term "human antibody" refers to antibodies in which substantially every portion of a protein (e.g., CDRs, framework, C L 、C H Domain (e.g., C H1 、C H2 、C H3), hinge, (VL, VH)) are substantially non-immunogenic in humans and have only minor sequence changes or variations. Similarly, antibodies designated as primates (monkeys, baboons, chimpanzees, etc.), rodents (mice, rats, rabbits, guinea pigs, hamsters, etc.) and other mammals refer to such species, subgenus, genus, subfamily, and family-specific antibodies. In addition, chimeric antibodies include any combination of the above. Relative to unmodified antibodies, such changes or alterations optionally retain or reduce immunogenicity in humans or other species. Therefore, human antibodies are different from chimeric or humanized antibodies. It should be noted that human antibodies can be produced by non-human animals or prokaryotic or eukaryotic cells capable of expressing functionally rearranged human immunoglobulin (e.g., heavy chain and / or light chain) genes. In addition, when the human antibody is a single-chain antibody, it can include a linker peptide that is not present in natural human antibodies. For example, Fv can include a linker peptide connecting the heavy chain variable region and the light chain variable region, such as 2 to about 8 glycine or other amino acid residues. This linker peptide is considered to be of human origin.

[0158] As used herein, if the antibody is obtained from a system using human immunoglobulin sequences, such as by immunizing transgenic mice carrying human immunoglobulin genes or by screening human immunoglobulin gene libraries, then the human antibody is "derived from" a specific germline sequence. Human antibodies "derived from" human germline immunoglobulin sequences can be identified by comparing the amino acid sequence of the human antibody with the amino acid sequence of human germline immunoglobulins. The selected human antibody typically has at least 90% identity with the amino acid sequence encoded by the human germline immunoglobulin gene in amino acid sequence, and when compared with the germline immunoglobulin amino acid sequence of other species (e.g., mouse germline sequence), the selected human antibody contains the amino acid residues that identify the human antibody as human. In some cases, the human antibody can have at least 95%, even at least 96%, 97%, 98% or 99% identity with the amino acid sequence encoded by the germline immunoglobulin gene in amino acid sequence. Typically, the difference between the amino acid sequence encoded by the human antibody and the human germline immunoglobulin gene for a specific human germline sequence is no more than 10 amino acids. In certain cases, the human antibody may display no more than 5, or even no more than 4, 3, 2, or 1 amino acid difference from the amino acid sequence encoded by the germline immunoglobulin gene.

[0159] As used herein, the term "humanized antibody" or "humanized immunoglobulin" refers to a human / non-human chimeric antibody that contains minimal sequence derived from a non-human immunoglobulin. In most cases, a humanized antibody is a human immunoglobulin (acceptor antibody) in which residues from the variable region or fragment thereof (e.g., 1, 2, 3, 4, 5 or all 6 CDRs) of the recipient are replaced with residues from a variable region or fragment thereof (e.g., 1, 2, 3, 4, 5 or all 6 CDRs) of a non-human species (donor antibody) (e.g., mouse, rat, rabbit or non-human primate) with the desired specificity, affinity and capacity. The humanized antibody may contain residues that are not found in the recipient antibody or the donor antibody. The humanized antibody may also optionally contain at least a portion of the constant region (Fc) of an immunoglobulin (usually a human immunoglobulin) at one or more amino acids in the framework region, constant region or CDR. In some embodiments, the humanized antibody is a non-human antibody in which an amino acid is replaced by an amino acid from the corresponding position of a human antibody. Without being bound by theory, compared with the non-humanized version of the same antibody, the humanized antibody produces a reduced immune response in the human host. Humanized antibodies can have conservative amino acid substitutions that are substantially unaffected by antigen binding or other antibody functions. Conservative substitution groupings include: glycine-alanine, valine-leucine-isoleucine, phenylalanine-tyrosine, lysine-arginine, alanine-valine, serine-threonine and asparagine-glutamine. Specifically, humanized antibodies as disclosed herein specifically bind to DNABII polypeptide or its fragment (such as head chimeric peptide or tail chimeric peptide) with one or more of the following specific ranges: EC 50 , K on , K off , K A and / or K D , and inhibit or release specific cytokines when treating a subject. In another embodiment, a humanized antibody that specifically binds to the head region of a DNABII polypeptide (e.g., a head chimeric peptide) destroys biofilms both in vivo and in vitro. In addition, the humanization process, although a rational design process, may produce unexpected changes (positive or negative) in, for example, binding affinity, antigen specificity, or physical properties (e.g., solubility or aggregation); therefore, the properties of a humanized antibody cannot be inherently predicted from the properties of the starting non-human antibody.

[0160] In one embodiment, the antibody as used herein can be a recombinant antibody. As used herein, the term "recombinant antibody" includes all antibodies prepared, expressed, produced or separated by a recombinant manner, such as antibodies isolated from transgenic or transchromosomal animals (e.g., mice) transfected with immunoglobulin genes or hybridomas prepared therefrom, antibodies isolated from host cells (e.g., transfectomas) transformed to express antibodies, antibodies isolated from recombinant combinatorial antibody libraries, and antibodies prepared, expressed, produced or separated by any other means involving splicing immunoglobulin (Ig) gene sequences to other DNA sequences. However, in certain embodiments, such recombinant antibodies can be subjected to in vitro mutagenesis (or, when using Ig sequence transgenic animals, in vivo somatic mutagenesis), so the amino acid sequences of the VH and VL regions of the recombinant antibodies may be sequences that are not naturally present in the antibody germline library in vivo. Methods for preparing these antibodies are described herein.

[0161] In one embodiment, an antibody as used herein may be a chimeric antibody. As used herein, a chimeric antibody is an antibody whose light and heavy chain genes are constructed, typically by genetic engineering, from antibody variable and constant region genes belonging to different species.

[0162] As used herein, the term "antibody derivative" includes full-length antibodies or antibody fragments in which one or more amino acids are chemically modified by alkylation, pegylation, acylation, ester formation, or amide formation, for example, to link the antibody to a second molecule. This includes, but is not limited to, pegylated antibodies, cysteine ​​pegylated antibodies, and variants thereof.

[0163] As used herein, the term "label" means a directly or indirectly detectable compound or component that is conjugated directly or indirectly to the composition to be detected, such as an N-terminal histidine tag (N-His), a magnetically active isotope, e.g., 115 Sn, 117 Sn and 119 Sn, non-radioactive isotopes, such as 13 C and 15N, polynucleotide or protein, such as antibody, to produce "label" component. The term also includes sequences conjugated to polynucleotides that provide signals when the expression of the inserted sequence is expressed, such as green fluorescent protein (GFP) etc. The label itself can be detectable (e.g., radioisotope labeling or fluorescent labeling), or in the case of enzyme labeling, can catalyze the chemical change of a detectable substrate compound or component. Labeling can be applicable to small-scale detection or more suitable for high-throughput screening. Therefore, suitable labels include but are not limited to magnetically active isotopes, non-radioactive isotopes, radioisotopes, fluorescent dyes, chemiluminescent compounds, dyes and proteins (including enzymes). Labeling can be simply detected or quantified. The response of a simple detection generally includes a response in which its presence is only confirmed, while a quantified response generally includes a response with a quantifiable (e.g., digitally reportable) value, such as intensity, polarization and / or other characteristics. In luminescence or fluorescence assays, detectable responses can be directly generated using a luminophore or fluorophore associated with the actual assay component involved in the combination, or indirectly generated using a luminophore or fluorophore associated with another (e.g., reporter molecule or indicator) component. Examples of luminescent labels that generate a signal include, but are not limited to, bioluminescence and chemiluminescence. A detectable luminescent response typically includes a change or appearance of a luminescent signal. Suitable methods and luminophores for luminescently labeling assay components are known in the art and are described, for example, in Haugland, Richard P. (1996) Handbook of Fluorescent Probes and Research Chemicals (1996). th Examples of luminescent probes include, but are not limited to, aequorin and luciferase.

[0164] As used herein, the term "immunoconjugate" includes an antibody or antibody derivative linked or attached to a second agent, such as a cytotoxic agent, a detectable agent, a radioactive agent, a targeting agent, a human antibody, a humanized antibody, a chimeric antibody, a synthetic antibody, a semisynthetic antibody, or a multispecific antibody.

[0165] Examples of suitable fluorescent labels include, but are not limited to, fluorescein, rhodamine, tetramethylrhodamine, eosin, erythrosine, coumarin, methylcoumarin, pyrene, malachite green, stilbene, Lucifer Yellow, Cascade Blue, TM and Texas Red. Other suitable optical dyes are described in Haugland, Richard P. (1996) Handbook of Fluorescent Probes and Research Chemicals (6th ed.).

[0166] In another aspect, fluorescent labeling is functionalized to promote the covalent attachment of cellular components (such as cell surface markers) present in or on the cell or tissue surface. Suitable functional groups include but are not limited to isothiocyanate groups, amino groups, haloacetyl groups, maleimide, succinimide esters and sulfonyl halides, all of which can be used to connect fluorescent labeling to the second molecule. The selection of fluorescent labeling functional groups will depend on the attachment site with joints, reagents, markers or the second labeling reagent.

[0167] "Eukaryotic cells" include all kingdoms of life except for the anucleate protozoa. They can be easily distinguished by their membrane-bound nuclei. Animals, plants, fungi, and protists are eukaryotic organisms or organisms whose cells are organized into a complex structure by an internal membrane and a cytoskeleton. The most characteristic membrane-bound structure is the nucleus. Unless otherwise specified, the term "host" includes eukaryotic hosts, including, for example, yeast, higher plants, insects, and mammalian cells. Non-limiting examples of eukaryotic cells or hosts include apes, cows, pigs, mice, rats, birds, reptiles, and humans.

[0168] "Prokaryotic cells" generally lack a nucleus or any other membrane-bound organelles and are divided into two domains, Bacteria and Archaea. In addition to chromosomal DNA, these cells can also contain genetic information in circular loops called episomes. Bacterial cells are very small, about the size of animal mitochondria (about 1-2 μm in diameter and about 10 μm long). Prokaryotic cells have three main shapes: rod-shaped, spherical, and spiral. Bacterial cells do not undergo the complex replication process like eukaryotic cells, but instead divide by binary fission. Examples include but are not limited to Bacillus, Escherichia coli, and Salmonella.

[0169] A "native" antigen is an epitope-containing polypeptide, protein or fragment isolated from a natural biological source that can specifically bind to an antigen receptor in a subject, particularly a T cell antigen receptor (TCR).

[0170] The terms "antigen" and "antigenicity" refer to a molecule that can be recognized by an antibody or otherwise act as a member of an antibody-ligand pair. "Specific binding" or "binding" refers to the interaction of an antigen with the variable regions of the heavy and light chains of an immunoglobulin. Antibody-antigen binding can occur in vivo or in vitro. Those skilled in the art will understand that macromolecules including proteins, nucleic acids, fatty acids, lipids, lipopolysaccharides and polysaccharides have the potential to act as antigens. Those skilled in the art will further understand that a nucleic acid encoding a protein with the potential to act as an antibody ligand necessarily encodes an antigen. Those skilled in the art will further understand that antigens are not limited to full-length molecules, but may also include partial molecules. The term "antigen" is an adjective for molecules that have antigenic properties. The term includes immunogenic substances, i.e., immunogens, as well as substances that induce immune unresponsiveness or anergy, i.e., allergens.

[0171] "Altered antigens" are antigens that have a primary sequence that differs from that of the corresponding wild-type antigen. Altered antigens can be prepared by synthetic or recombinant methods, including but not limited to antigenic peptides that are differentially modified during or after translation, such as by phosphorylation, glycosylation, cross-linking, acylation, proteolytic cleavage, or attachment to antibody molecules, membrane molecules, or other ligands. (Ferguson et al. (1988) Ann. Rev. Biochem. 57: 285-320). Synthetic or altered antigens disclosed herein are intended to bind to the same TCR as the native epitope.

[0172] "Autoantigens," also referred to herein as natural or wild-type antigens, refer to antigenic peptides that induce little or no immune response in a subject due to self-tolerance to the antigen. An example of an autoantigen is the melanoma-specific antigen gp100.

[0173] "Immune response" generally refers to the antigen-specific response of lymphocytes to foreign substances. The terms "immunogen" and "immunogenicity" refer to molecules that have the ability to elicit an immune response. All immunogens are antigens, however, not all antigens are immunogenic. The immune response disclosed herein can be humoral (through antibody activity) or cell-mediated (through T cell activation). The response may occur in vivo or in vitro. Those skilled in the art will understand that a variety of macromolecules, including proteins, nucleic acids, fatty acids, lipids, lipopolysaccharides and polysaccharides have the potential to be immunogenic. Those skilled in the art will further understand that nucleic acids encoding molecules capable of eliciting an immune response necessarily encode immunogens. Those skilled in the art will further understand that immunogens are not limited to full-length molecules, but may include partial molecules.

[0174] The term "passive immunity" refers to the transfer of immunity from one subject to another through antibody transfer. Passive immunity may occur naturally, as when maternal antibodies are transferred to a fetus. Passive immunity can also occur artificially when an antibody composition is administered to a non-immune subject. The antibody donor and recipient can be human or non-human subjects. Antibodies can be polyclonal or monoclonal, can be produced in vitro or in vivo, and can be purified, partially purified, or unpurified depending on the embodiment. In some embodiments described herein, passive immunity is conferred to a subject in need by administering an antibody or antigen-binding fragment that specifically recognizes or binds to a specific antigen. In some embodiments, passive immunity is conferred by administering an isolated or recombinant polynucleotide encoding an antibody or antigen-binding fragment that specifically recognizes or binds to a specific antigen.

[0175] In the context of this disclosure, a "ligand" is a polypeptide. In one aspect, the term "ligand," as used herein, refers to any molecule that binds to a specific site on another molecule. In other words, the ligand confers specificity to the protein in its reaction with immune effector cells, antibodies against the protein, or DNA against the protein. In one aspect, a ligand site within a protein binds directly to a complementary binding site on an immune effector cell.

[0176] As used herein, "solid support" or "solid support" used interchangeably are not limited to a particular type of support. Rather, a large number of supports are known and available to those of ordinary skill in the art. Solid supports include silica gel, resins, derivatized plastic films, glass beads, cotton, plastic beads, alumina gel. As used herein, "solid support" also includes synthetic antigen presenting matrices, cells, and liposomes. Suitable solid supports can be selected based on the desired end use and suitability for various protocols. For example, for peptide synthesis, a solid support can refer to a resin, such as polystyrene (e.g., PAM-resin available from Bachem Inc., Peninsula Laboratories, etc.), resin (obtained from Aminotech, Canada), polyamide resin (obtained from Peninsula Laboratories), polystyrene resin grafted with polyethylene glycol ( Rapp Polymere, Tubingen, Germany) or polydimethylacrylamide resin (obtained from Milligen / Biosearch, CA).

[0177] Examples of solid supports include glass, polystyrene, polypropylene, polyethylene, dextran, nylon, amylase, natural and modified cellulose, polyacrylamide, gabbro and magnetite. The nature of the carrier can be soluble or insoluble to a certain extent. The support material can have virtually any possible structural configuration, as long as the coupled molecule is capable of binding to the polynucleotide, polypeptide or antibody. Thus, the support structure can be spherical, such as beads, or cylindrical, such as the inner surface of a test tube or the outer surface of a rod. Alternatively, the surface can be flat, such as a sheet, test strips, etc., or polystyrene beads. Those skilled in the art will know many other carriers suitable for binding antibodies or antigens, or will be able to determine these carriers by using routine experiments.

[0178] As used herein, biological samples or samples can be obtained from a subject, cell line, or cultured cells or tissue. Exemplary samples include, but are not limited to, cell samples, tissue samples, liquid samples such as blood and other biologically derived liquid samples (including but not limited to ocular fluid (aqueous humor and vitreous humor), peripheral blood, serum, plasma, ascites, urine, cerebrospinal fluid (CSF), sputum, saliva, bone marrow, synovial fluid, aqueous humor, amniotic fluid, cerumen, breast milk, bronchoalveolar lavage fluid, semen, prostatic fluid, Cowper's fluid or pre-ejaculatory fluid, female ejaculation, sweat, tears, cystic fluid, pleural effusion, pericardial fluid, ascites, lymphatic fluid, chyme, chyle, bile, interstitial fluid, menstruation, pus, sebum, vomitus, vaginal secretions / washing fluid, synovial fluid, mucosal secretions, fecal water, pancreatic juice, lavage fluid from the sinus cavity, bronchopulmonary aspirate, blastocyst cavity fluid, or umbilical cord blood. In one embodiment, the biological sample is suspected of having a biofilm. In another embodiment, the biological sample includes a biofilm.

[0179] As used herein, the term "signal peptide" or "signal polypeptide" refers to an amino acid sequence that is typically present at the N-terminus of a newly synthesized secretory or membrane polypeptide or protein. Its function is to direct the polypeptide to a specific cellular location, such as through the cell membrane, into the cell membrane, or into the cell nucleus. In some embodiments, the signal peptide is removed after localization. Examples of signal peptides are well known in the art. Non-limiting examples are those described in U.S. Patent Nos. 8,853,381, 5,958,736, and 8,795,965.

[0180] As used herein, the term "chimera" or "chimeric peptide" refers to a recombinant polypeptide comprising two or more fragments or domains of a DNABII polypeptide that are directly or indirectly (e.g., via a linker) conjugated to each other, or consisting essentially of, or consisting of. In one embodiment, these domains are conformational head domains and / or conformational tail domains. In addition or alternatively, these two or more fragments or domains are derived from the same or different DNABII polypeptides. In one embodiment, the chimeric peptide comprises an IhfA head domain and an IhfB head domain that are directly or indirectly (e.g., via a linker) conjugated to each other, or consisting essentially of, or consisting of. In another embodiment, the chimeric peptide comprises an IhfA tail domain and an IhfB tail domain that are directly or indirectly (e.g., via a linker) conjugated to each other, or consisting essentially of, or consisting of. The "conformation head domain" of a polypeptide refers to a polypeptide comprising a primary amino acid sequence wherein the structure has antiparallel β bands having sharp turns typically mediated by proline residues. The "head" of an IHF polypeptide is shown in the referenced portion of WO2018 / 129078. Figure 1 middle.

[0181] In certain embodiments, the head chimeric peptide IhfA5-mIhfB4NTHI comprising, consisting essentially of, or consisting of the following polypeptide sequence: RPGRNPX1TGDVVPVSARRVV-X-FSLHHRQPRLGRNPX1TGDSV (SEQ ID NO: 38), wherein "X" is an optional amino acid linker sequence, optionally comprising (or consisting essentially of, or consisting of) 1 to 20 amino acids; and wherein "X1" is any amino acid, or "X1" is selected from amino acids Q, R, K, S or T. In another aspect, "X1" is K or Q. In a further embodiment, the head chimeric peptide IhfA5-mIhfB4 NTHI comprising, consisting essentially of, or consisting of the following polypeptide sequence: RPGRNPKTGDVVPVSARRVV-X-FSLHHRQPRLGRNPKTGDSV (SEQ ID NO: 39), wherein "X" is an optional amino acid linker sequence, optionally comprising (or consisting essentially of, or consisting of) 1 to 20 amino acids. In a further embodiment, the head chimeric peptide IhfA5-mIhfB4 NTHI Comprising, consisting essentially of, or consisting of the following polypeptide sequence:

[0182]

[0183] In certain embodiments, the tail chimeric peptide IhfA3-IhfB2 NTHI The polypeptide sequence comprises, consists essentially of, or consists of the following polypeptide sequence: FLEEIRLSLESGQDVKLSGF-X-TLSAKEIENMVKDILEFISQ (SEQ ID NO: 41), wherein "X" is an optional amino acid linker sequence, optionally comprising (or consisting essentially of, or consisting of) 1 to 20 amino acids. In certain embodiments, the linker is selected from any one or more of SEQ ID NOs: 42-49. In one embodiment, the tail chimeric peptide IhfA3-IhfB2 NTHI Comprising, consisting essentially of, or consisting of the following polypeptide sequence:

[0184] FLEEIRLSLESGQDVKLSGFGPSLTLSAKEIENMVKDILEFISQ (SEQ ID NO: 50).

[0185] As used herein, the term "EC 50 ” refers to the concentration of an antibody or fragment thereof that induces a response (e.g., binding between the antibody or fragment thereof and its target) that is intermediate between baseline and maximum after a specified exposure time.

[0186] Several parameters are used herein to describe the binding and dissociation reactions of receptor (R, such as an antibody or fragment thereof) and ligand (L, such as the target of the antibody or fragment thereof) molecules, which are formalized as follows: The reaction is characterized by an association rate constant k on and the dissociation rate constant k off To represent, its units are M -1 s -1 and s -1 In equilibrium, the forward binding transition R+L→RL should be balanced by the reverse non-binding transition RL→R+L. on [R][L]=k off [RL], where [R], [L], and [RL] represent the concentration of unbound free receptor, the concentration of unbound free ligand, and the concentration of receptor-ligand complex. In addition, the equilibrium dissociation constant "K D ” can be calculated as k off / k on , that is, [R]x[L] /

[0187] [RL], and the equilibrium association constant "K A ” can be calculated as k on / k off , that is [RL] / ([R]x[L].

[0188] As used herein, the term "cytokine" refers to a small protein (about 5-20 kDa) that is important in cell signaling, including but not limited to chemokines, interferons, interleukins (IL), lymphokines and tumor necrosis factors, but generally does not include hormones. Cytokines are peptides that cannot pass through the lipid bilayer of the cell to enter the cytoplasm. Inflammatory cytokines or proinflammatory cytokines are signaling molecules (cytokines) that are secreted by immune cells such as helper T cells (Th) and macrophages, as well as certain other cell types that promote inflammation. They include (but are not limited to) interleukin-1 (IL-1), IL-12 and IL-18, tumor necrosis factor alpha (TNF-α), interferon gamma (IFNγ) and granulocyte-macrophage colony-stimulating factor (GM-CSF) and play an important role in mediating innate immune responses. Inflammatory cytokines are mainly produced by and participate in the upregulation of inflammatory responses. The term "anti-inflammatory cytokines" includes immunomodulatory molecules that control proinflammatory cytokine responses. Cytokines work together with specific cytokine inhibitors and soluble cytokine receptors to regulate the body's immune response. The main anti-inflammatory cytokines include interleukin (IL)-1 receptor antagonists, IL-

[0189] 4, IL-6, IL-10, IL-11, and IL-13. Specific cytokine receptors for IL-1, tumor necrosis factor-α, and IL-18 can also serve as inhibitors of proinflammatory cytokines. Methods for measuring cytokine levels (including anti-inflammatory and proinflammatory cytokines) are well known in the art. For example, serum cytokine levels can be measured using commercially available enzyme-linked immunosorbent assay (ELISA) kits.

[0190] As used herein, the term "anti-infective" refers to a drug that can inhibit the spread of infectious organisms or completely kill infectious organisms. The term includes, but is not limited to, antibiotics, antifungals, anthelmintics, antimalarials, antiprotozoals, antituberculosis drugs, and antivirals. Antifungals are also known as antimycotics. They kill or inactivate fungi and are used to treat fungal infections (including yeast infections). As a non-limiting example, polyene antifungals are not absorbed when taken orally and are therefore used to treat fungal infections of the gastrointestinal tract, such as thrush. Another non-limiting example is the azole antifungal agents, which are synthetic antifungal agents with broad-spectrum activity. The echinocandins are lipopeptide molecules that non-competitively inhibit (1,3)β-d-glucan synthase and target the fungal cell wall. These include fulvicin U / F (i.e., griseofulvin), Grifulvin V(Pro) (i.e., griseofulvin), Lamisil(Pro) (i.e., terbinafine), Gris-PEG(Pro) (i.e., griseofulvin), Ancobon(Pro) (i.e., flucytosine), Fuvicin P / G (i.e., griseofulvin), and Terbinex(Pro) (i.e., terbinafine). More anti-infective drugs can be found, for example, at www.drugbank.ca / categories / DBCAT000065. The term "antiviral" refers to a class of drugs used to treat viral infections. While most antiviral drugs target specific viruses, broad-spectrum antiviral drugs are effective against a wide range of viruses. Unlike most antibiotics, antiviral drugs do not destroy their target pathogens; instead, they inhibit their development. Some of the ways they may work include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of viral assembly.

[0191] Non-limiting examples of antiviral agents can be found at www.drugbank.ca / categories / DBCAT000066.

[0192] As used herein, the term "antiparasitic drug" refers to a class of drugs used to treat parasitic diseases, such as those caused by helminths, amoebae, ectoparasites, parasitic fungi, protozoa, etc. Non-limiting examples of antiparasitic drugs can be found, for example, at www.drugbank.ca / categories / DBCAT000522.

[0193] Modes for carrying out the present disclosure

[0194] Antibody composition

[0195] The present disclosure provides a kind of antibody of separation, it comprises heavy chain (HC) variable domain sequence and light chain (LC) variable domain sequence, wherein heavy chain and light chain immunoglobulin variable domain sequence form antigen binding site, it combines the epitope of DNABII protein.In certain embodiments, antibody or its fragment combines DNABII peptide (for example DNABII peptide head region, including but not limited to: IHF or HU head region, IHFA or IHFB head region, and / or head chimeric peptide IhfA5-mIhfB4 NTHI and / or the tail region of a DNABII peptide, including but not limited to: the tail region of IHF or HU, the tail region of IHFA or IHFB, and / or the tail chimeric peptide IhfA3-IhfB2 NTHI In one embodiment, the antibody or fragment thereof binds to the head chimeric peptide IhfA5-mIhfB4 NTHI In another embodiment, the antibody or fragment thereof binds to the tail chimeric peptide IhfA3-IhfB2 NTHI .

[0196] In one aspect, provided herein are antibodies or antigen-binding fragments thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of a sequence selected from aa 25 to aa 144 of SEQ ID NO: 1-6, 13, 24 or 26, or an equivalent of each thereof, and / or a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of a sequence selected from aa 21 to aa 132 of SEQ ID NO: 7-9, 14 or 25, aa 21 to aa 132 of SEQ ID NO: 10-12 or 27, or an equivalent of each thereof.

[0197] In another aspect, provided herein are antibodies or antigen-binding fragments thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) comprising, consisting essentially of, or consisting of a sequence selected from aa 25 to aa 473 of SEQ ID NO: 1-6, 13, 24 or 26, or an equivalent of each thereof, and / or a light chain (LC) comprising, consisting essentially of, or consisting of a sequence selected from aa 21 to aa 239 of SEQ ID NO: 7-9, 14 or 25, aa 21 to aa 233 of SEQ ID NO: 10-12 or 27, or an equivalent of each thereof.

[0198] In another aspect, provided herein is an antibody or antigen-binding fragment thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) comprising, consisting essentially of, or consisting of a sequence selected from SEQ ID NO: 1-6, 13, 24 or 26, or an equivalent of each thereof, and / or a light chain (LC) comprising, consisting essentially of, or consisting of a sequence selected from SEQ ID NO: 7-12, 14, 25 or 27, or an equivalent of each thereof.

[0199] In another aspect, provided herein are antibodies or antigen-binding fragments thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising a sequence of amino acids (aa) 25 to 144 selected from SEQ ID NOs: 1-6, 13, 24, or 26, or an equivalent of each thereof, and / or a light chain (LC) immunoglobulin variable domain sequence comprising aa 21 to aa 24 selected from SEQ ID NOs: 6-9, 14, or 25, or an equivalent of each thereof.

[0200] 132. The sequence of aa 21 to aa 126 of SEQ ID NO: 10-12 or 27, or an equivalent thereof, or consisting essentially of the same, or consisting of the same.

[0201] In another aspect, provided herein is an antibody or antigen-binding fragment thereof comprising, consisting essentially of, or consisting of the following CDR sequences: any one, any two or all three CDRs of a sequence selected from SEQ ID NO: 1-6, 13, 24 or 26, or an equivalent of each thereof; and / or any one, any two or all three CDRs of a sequence selected from SEQ ID NO: 7-12, 14, 25 or 27, or an equivalent of each thereof.

[0202] In another aspect, provided herein are antibodies or antigen-binding fragments thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of a sequence selected from aa 25 to aa 144 of SEQ ID NO: 13, 24 or 26, or an equivalent of each thereof, and a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of a sequence selected from aa 21 to aa 132 of SEQ ID NO: 14 or 25, aa 21 to aa 126 of SEQ ID NO: 27, or an equivalent of each thereof. In another aspect, provided herein are antibodies or antigen-binding fragments thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of a sequence selected from aa 25 to aa 144 of SEQ ID NO: 1-6, 13, 24 or 26, or an equivalent of each thereof, and / or a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of a sequence selected from aa 21 to aa 132 of SEQ ID NO: 7-9, 14 or 25, aa 21 to aa 126 of SEQ ID NO: 10-12 or 27, or an equivalent of each thereof.

[0203] Also provided herein are antibodies or antigen-binding fragments thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of an amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 1, or an equivalent thereof, and a light chain (LC) immunoglobulin variable domain sequence comprising

[0204] Any one of the amino acid sequences of aa 21 to aa 132 of SEQ ID NOs: 7-9, 14, or 25, aa 21 to aa126 of SEQ ID NOs: 10-12, or 27, or an equivalent thereof, or consisting essentially of, or consisting of. In another aspect, provided herein is an antibody or antigen-binding fragment thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of an amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 2, or an equivalent thereof, and a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of an amino acid sequence of aa 21 to aa132 of SEQ ID NO: 7-9, 14, or 25, aa 21 to aa126 of SEQ ID NO: 10-12, or 27, or an equivalent thereof. In another aspect, the present invention also provides an antibody or antigen-binding fragment thereof, which comprises, consists essentially of, or consists of a heavy chain (HC) immunoglobulin variable domain sequence and a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises the amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 3 or an equivalent thereof, or consists essentially of, or consists of it, and the LC immunoglobulin variable domain sequence comprises, consists essentially of, or consists of any one of the amino acid sequences of aa 21 to aa 132 of SEQ ID NO: 7-9, 14 or 25, aa 21 to aa126 of SEQ ID NO: 10-12 or 27, or an equivalent of each thereof.

[0205] In another aspect, provided herein are antibodies or antigen-binding fragments thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of an amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 4, or an equivalent thereof, and a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of an amino acid sequence of aa 21 to aa 132 of SEQ ID NO: 7-9, 14, or 25, aa 21 to aa 126 of SEQ ID NO: 10-12, or 27, or an equivalent thereof. Provided herein are antibodies or antigen-binding fragments thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 5, or an equivalent thereof, and a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 21 to aa 132 of SEQ ID NO: 7-9, 14, or 25, aa21 to aa 126 of SEQ ID NO: 10-12, or 27, or an equivalent thereof. Provided herein are antibodies or antigen-binding fragments thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 6, or an equivalent thereof, and a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 21 to aa 132 of SEQ ID NO: 7-9, 14, or 25, aa 21 to aa 126 of SEQ ID NO: 10-12, or 27, or an equivalent thereof.

[0206] In another aspect, provided herein are antibodies or antigen-binding fragments thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 25 to aa 144 of any one of SEQ ID NOs: 1-6, 13, 24, or 26, or an equivalent of each thereof, and a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 21 to aa 132 of SEQ ID NO: 7, or an equivalent thereof. Provided herein are antibodies or antigen-binding fragments thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 25 to aa 144 of any one of SEQ ID NOs: 1-6, 13, 24, or 26, or an equivalent of each thereof, and a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 21 to aa 132 of SEQ ID NO: 8, or an equivalent thereof. In another aspect, provided herein are antibodies or antigen-binding fragments thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 25 to aa 144 of any one of SEQ ID NOs: 1-6, 13, 24, or 26, or an equivalent of each thereof, and a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 21 to aa 132 of SEQ ID NO: 9, or an equivalent thereof.

[0207] In another aspect, provided herein is an antibody or antigen-binding fragment thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 25 to aa 144 of any one of SEQ ID NO: 1-6, 13, 24 or 26, or an equivalent of each thereof, and a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 21 to aa 126 of SEQ ID NO: 10, or an equivalent thereof. Provided herein are antibodies or antigen-binding fragments thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 25 to aa 144 of any one of SEQ ID NOs: 1-6, 13, 24, or 26, or an equivalent of each thereof; and a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 21 to aa 126 of SEQ ID NO: 11, or an equivalent thereof. Provided herein are antibodies or antigen-binding fragments thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 25 to aa 144 of any one of SEQ ID NOs: 1-6, 13, 24, or 26, or an equivalent of each thereof, and a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 21 to aa 126 of SEQ ID NO: 12, or an equivalent thereof.

[0208] In another aspect, provided herein are antibodies or antigen-binding fragments thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 1, or an equivalent thereof, and a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 21 to aa 132 of SEQ ID NO: 7, or an equivalent thereof. In one embodiment, provided herein is an antibody or antigen-binding fragment thereof comprising, or consisting essentially of, or consisting of, a heavy chain (HC) immunoglobulin variable domain sequence comprising, or consisting essentially of, or consisting of, the amino acid sequence of aa25 to aa 144 of SEQ ID NO: 1, or an equivalent thereof, and a light chain (LC) immunoglobulin variable domain sequence comprising, or consisting essentially of, or consisting of, the amino acid sequence of aa 21 to aa132 of SEQ ID NO: 8, or an equivalent thereof. In another embodiment, provided herein is an antibody or antigen-binding fragment thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 1, or an equivalent thereof, and a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 21 to aa 132 of SEQ ID NO: 9, or an equivalent thereof.

[0209] In another aspect, provided herein are antibodies or antigen-binding fragments thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 2, or an equivalent thereof, and a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 21 to aa 132 of SEQ ID NO: 7, or an equivalent thereof. In another aspect, provided herein are antibodies or antigen-binding fragments thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 2, or an equivalent thereof, and a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 21 to aa 132 of SEQ ID NO: 8, or an equivalent thereof. In another aspect, provided herein is an antibody or antigen-binding fragment thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 2, or an equivalent thereof, and a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 21 to aa 132 of SEQ ID NO: 9, or an equivalent thereof.

[0210] In another aspect, provided herein are antibodies or antigen-binding fragments thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 3, or an equivalent thereof, and a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 21 to aa 132 of SEQ ID NO: 7, or an equivalent thereof. In another aspect, provided herein are antibodies or antigen-binding fragments thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 3, or an equivalent thereof, and a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 21 to aa 132 of SEQ ID NO: 8, or an equivalent thereof. In one embodiment, provided herein is an antibody or antigen-binding fragment thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising the amino acid sequence of aa 25 to aa 144 of SEQ ID NO:3, or an equivalent thereof, or consisting essentially of, or consisting of, a light chain (LC) immunoglobulin variable domain sequence comprising the amino acid sequence of aa 21 to aa 132 of SEQ ID NO:9, or an equivalent thereof, or consisting essentially of, or consisting of.

[0211] Also provided herein are antibodies or antigen-binding fragments thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of an amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 4, or an equivalent thereof, and a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of

[0212] The amino acid sequence of aa 21 to aa 126 of SEQ ID NO: 10, or an equivalent thereof, or consisting essentially thereof, or consisting of. In another aspect, also provided herein is an antibody or antigen-binding fragment thereof, which comprises, consists essentially of, or consists of a heavy chain (HC) immunoglobulin variable domain sequence and a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises, consists essentially of, or consists of the amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 4, or an equivalent thereof, or consists essentially of, or consists of, the LC immunoglobulin variable domain sequence comprises, consists essentially of, or consists of the amino acid sequence of aa 21 to aa 126 of SEQ ID NO: 11, or an equivalent thereof. In another aspect, the present invention also provides an antibody or antigen-binding fragment thereof, which comprises a heavy chain (HC) immunoglobulin variable domain sequence and a light chain (LC) immunoglobulin variable domain sequence, or consists essentially of, or consists of, wherein the HC immunoglobulin variable domain sequence comprises the amino acid sequence of aa 25 to aa 144 of SEQ ID NO:4 or an equivalent thereof, or consists essentially of, or consists of, and the LC immunoglobulin variable domain sequence comprises the amino acid sequence of aa 21 to aa126 of SEQ ID NO:12 or an equivalent thereof, or consists essentially of, or consists of.

[0213] In one embodiment, provided herein is an antibody or antigen-binding fragment thereof comprising, or consisting essentially of, or consisting of, a heavy chain (HC) immunoglobulin variable domain sequence comprising the amino acid sequence of aa 25 to aa 144 of SEQ ID NO:5, or an equivalent thereof, or consisting essentially of, or consisting of, a light chain (LC) immunoglobulin variable domain sequence comprising the amino acid sequence of aa 21 to aa 126 of SEQ ID NO:10, or an equivalent thereof, or consisting essentially of, or consisting of. In another embodiment, provided herein is an antibody or antigen-binding fragment thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 25 to aa 144 of SEQ ID NO:5, or an equivalent thereof, and a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 21 to aa 126 of SEQ ID NO:11, or an equivalent thereof. In another aspect, provided herein are antibodies or antigen-binding fragments thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 5, or an equivalent thereof, and a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 21 to aa 126 of SEQ ID NO: 12, or an equivalent thereof.

[0214] In another embodiment, provided herein is an antibody or antigen-binding fragment thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 6, or an equivalent thereof, and a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 21 to aa 126 of SEQ ID NO: 10, or an equivalent thereof. In one aspect, provided herein are antibodies or antigen-binding fragments thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa25 to aa 144 of SEQ ID NO: 6, or an equivalent thereof, and a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 21 to aa 126 of SEQ ID NO: 11, or an equivalent thereof. In one embodiment, provided herein is an antibody or antigen-binding fragment thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 6, or an equivalent thereof, and a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 21 to aa 126 of SEQ ID NO: 12, or an equivalent thereof.

[0215] In one aspect, provided herein is an antibody or its fragment, it includes heavy chain (HC) immunoglobulin variable domain sequence and / or light chain (LC) immunoglobulin variable domain sequence, or substantially consisting of it, or consisting of it, the HC immunoglobulin variable domain sequence includes SEQ ID NO:24 aa 25 to aa 144 amino acid sequence or its equivalent, or substantially consisting of it, or consisting of it, the LC immunoglobulin variable domain sequence includes SEQ ID NO:25 aa 21 to aa 132 amino acid sequence or its equivalent, or substantially consisting of it, or consisting of it. In one embodiment, the antibody or its fragment binds to the head region of DNABII peptide (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB, and / or head chimeric peptide IhfA5-mIhfB4 NTHIIn one embodiment, the antibody or fragment thereof binds to the head chimeric peptide IhfA5-mIhfB4 NTHI . In another embodiment, the fragment is an antigen-binding fragment. In one embodiment, provided herein is an antibody or fragment thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of the amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 1, or an equivalent thereof, or consisting essentially of, or consisting of, a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of, the amino acid sequence of aa 21 to aa 132 of SEQ ID NO: 7, or an equivalent thereof. In another embodiment, provided herein are antibodies or fragments thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of an amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 1 or an equivalent thereof, and / or a light chain (LC) immunoglobulin variable domain sequence comprising:

[0216] The amino acid sequence of aa 21 to aa 132 of SEQ ID NO: 8, or an equivalent thereof, or consisting essentially thereof. In another embodiment, provided herein are antibodies or fragments thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of an amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 1, or an equivalent thereof, and / or a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consisting of an amino acid sequence of aa 21 to aa 132 of SEQ ID NO: 9, or an equivalent thereof. In one embodiment, provided herein are antibodies or fragments thereof comprising, or consisting essentially of, or consisting of, a heavy chain (HC) immunoglobulin variable domain sequence comprising the amino acid sequence of aa25 to aa 144 of SEQ ID NO:2 or an equivalent thereof, or consisting essentially of, or consisting of, a light chain (LC) immunoglobulin variable domain sequence comprising the amino acid sequence of aa 21 to aa 132 of SEQ ID NO:7 or an equivalent thereof, or consisting essentially of, or consisting of. In another embodiment, the antibody or fragment thereof comprises, or consists essentially of, or consists of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises the amino acid sequence of aa 25 to aa 144 of SEQ ID NO:2 or an equivalent thereof, or consists essentially of, or consists of, and the LC immunoglobulin variable domain sequence comprises the amino acid sequence of aa 21 to aa 132 of SEQ ID NO:8 or an equivalent thereof, or consists essentially of, or consists of. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises the amino acid sequence of aa 25 to aa 144 of SEQ ID NO:2 or an equivalent thereof, or consists essentially of, or consists of, and the LC immunoglobulin variable domain sequence comprises the amino acid sequence of aa 21 to aa 132 of SEQ ID NO:9 or an equivalent thereof, or consists essentially of, or consists of.In one embodiment, the antibody or fragment thereof comprises, or consists essentially of, or consists of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises the amino acid sequence of aa 25 to aa 144 of SEQ ID NO:3 or an equivalent thereof, or consists essentially of, or consists of, and the LC immunoglobulin variable domain sequence comprises the amino acid sequence of aa 21 to aa132 of SEQ ID NO:7 or an equivalent thereof, or consists essentially of, or consists of. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises the amino acid sequence of aa 25 to aa 144 of SEQ ID NO:3 or an equivalent thereof, or consists essentially of, or consists of, and the LC immunoglobulin variable domain sequence comprises the amino acid sequence of aa 21 to aa 132 of SEQ ID NO:8 or an equivalent thereof, or consists essentially of, or consists of. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises the amino acid sequence of aa 25 to aa 144 of SEQ ID NO:3 or an equivalent thereof, or consists essentially of, or consists of, and the LC immunoglobulin variable domain sequence comprises the amino acid sequence of aa 21 to aa 132 of SEQ ID NO:9 or an equivalent thereof, or consists essentially of, or consists of.

[0217] On the other hand, there is provided herein an antibody or its fragment, it includes heavy chain (HC) immunoglobulin variable domain sequence and light chain (LC) immunoglobulin variable domain sequence, or substantially consisting of it, or consisting of it, the HC immunoglobulin variable domain sequence includes SEQ ID NO:26 aa 25 to aa 144 amino acid sequence or its equivalent, or substantially consisting of it, or consisting of it, the LC immunoglobulin variable domain sequence includes SEQ ID NO:27 aa 21 to aa 126 amino acid sequence or its equivalent, or substantially consisting of it, or consisting of it. In another embodiment, the antibody or its fragment is bound to the tail region of DNABII peptide (including but not limited to the tail region of IHF or HU, the tail region of IHFA or IHFB and / or tail chimeric peptide IhfA3-IhfB2 NTHIIn one embodiment, the antibody or fragment thereof binds to the tail chimeric peptide IhfA3-IhfB2 NTHI. In another embodiment, the fragment is an antigen-binding fragment. In one embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises the amino acid sequence of aa 25 to aa 144 of SEQ ID NO:4 or an equivalent thereof, or consists essentially of, or consists of, the LC immunoglobulin variable domain sequence comprises the amino acid sequence of aa 21 to aa126 of SEQ ID NO:10 or an equivalent thereof, or consists essentially of, or consists of. In another embodiment, the fragment is an antigen-binding fragment. In one embodiment, the antibody or fragment thereof comprises, or consists essentially of, or consists of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises the amino acid sequence of aa25 to aa 144 of SEQ ID NO:4 or an equivalent thereof, or consists essentially of, or consists of, and the LC immunoglobulin variable domain sequence comprises the amino acid sequence of aa 21 to aa 126 of SEQ ID NO:11 or an equivalent thereof, or consists essentially of, or consists of. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises the amino acid sequence of aa 25 to aa 144 of SEQ ID NO:4 or an equivalent thereof, or consists essentially of, or consists of, and the LC immunoglobulin variable domain sequence comprises the amino acid sequence of aa 21 to aa 126 of SEQ ID NO:12 or an equivalent thereof, or consists essentially of, or consists of. In one embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises the amino acid sequence of aa 25 to aa 144 of SEQ ID NO:5 or an equivalent thereof, or consists essentially of, or consists of, and the LC immunoglobulin variable domain sequence comprises the amino acid sequence of aa 21 to aa 126 of SEQ ID NO:10 or an equivalent thereof, or consists essentially of, or consists of. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises

[0218] The amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 5, or an equivalent thereof, or consists essentially thereof, and the LC immunoglobulin variable domain sequence comprises, consists essentially thereof, or consists of the amino acid sequence of aa 21 to aa 126 of SEQ ID NO: 11, or an equivalent thereof. In another embodiment, the antibody or fragment thereof comprises, consists essentially thereof, or consists of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, and the HC immunoglobulin variable domain sequence comprises, consists essentially thereof, or consists of the amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 5, or an equivalent thereof, or consists essentially thereof, and the LC immunoglobulin variable domain sequence comprises, consists essentially thereof, or consists of the amino acid sequence of aa 21 to aa 126 of SEQ ID NO: 12, or an equivalent thereof. In one embodiment, the antibody or fragment thereof comprises, or consists essentially of, or consists of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises the amino acid sequence of aa 25 to aa 144 of SEQ ID NO:6 or an equivalent thereof, or consists essentially of, or consists of, and the LC immunoglobulin variable domain sequence comprises the amino acid sequence of aa21 to aa 126 of SEQ ID NO:10 or an equivalent thereof, or consists essentially of, or consists of. In another embodiment, the antibody or fragment thereof comprises, or consists essentially of, or consists of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises the amino acid sequence of aa 25 to aa 144 of SEQ ID NO:6 or an equivalent thereof, or consists essentially of, or consists of, and the LC immunoglobulin variable domain sequence comprises the amino acid sequence of aa 21 to aa126 of SEQ ID NO:11 or an equivalent thereof, or consists essentially of, or consists of. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises the amino acid sequence of aa 25 to aa 144 of SEQ ID NO:5 or an equivalent thereof, or consists essentially of, or consists of, and the LC immunoglobulin variable domain sequence comprises the amino acid sequence of aa 21 to aa 126 of SEQ ID NO:12 or an equivalent thereof, or consists essentially of, or consists of.

[0219] In one aspect, there is provided herein an antibody or its fragment, it includes heavy chain (HC) and / or light chain (LC), or is substantially composed of it, or is composed of it, the HC includes SEQ ID NO:24 amino acid sequence or its equivalent, or is substantially composed of it, or is composed of it, the LC includes SEQ ID NO:25 amino acid sequence or its equivalent, or is substantially composed of it, or is composed of it. In another embodiment, the antibody or its fragment is bound to the head region of DNABII peptide (including but not limited to the head region of IHF or HU, the head region of IHFA or IHFB and / or head chimeric peptide IhfA5-mIhfB4 NTHI In one embodiment, the antibody or fragment thereof binds to the head chimeric peptide IhfA5-mIhfB4 NTHI. In another embodiment, the fragment is an antigen-binding fragment. In one embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) and / or a light chain (LC), the HC comprising the amino acid sequence of SEQ ID NO: 1 or an equivalent thereof, or consisting essentially of, or consisting of, the LC comprising the amino acid sequence of SEQ ID NO: 7 or an equivalent thereof, or consisting essentially of, or consisting of. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) and / or a light chain (LC), the HC comprising the amino acid sequence of SEQ ID NO: 1 or an equivalent thereof, or consisting essentially of, or consisting of, the LC comprising the amino acid sequence of SEQ ID NO: 8 or an equivalent thereof, or consisting essentially of, or consisting of. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 1 or an equivalent thereof, and / or a light chain (LC) comprising, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 9 or an equivalent thereof. In one embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 2 or an equivalent thereof, and / or a light chain (LC) comprising, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 7 or an equivalent thereof. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 2 or an equivalent thereof, and / or a light chain (LC) comprising, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 8 or an equivalent thereof. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 2 or an equivalent thereof, and / or a light chain (LC) comprising, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 9 or an equivalent thereof. In one embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) and / or a light chain (LC), wherein the HC comprises the amino acid sequence of SEQ ID NO:3 or an equivalent thereof, or consists essentially of, or consists of, and the LC comprises the amino acid sequence of SEQ ID NO:7 or an equivalent thereof, or consists essentially of, or consists of.In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 3 or an equivalent thereof, and / or a light chain (LC) comprising, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 8 or an equivalent thereof. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 3 or an equivalent thereof, and / or a light chain (LC) comprising, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 9 or an equivalent thereof.

[0220] In yet another aspect, there is provided herein an antibody or fragment thereof, which includes a heavy chain (HC) and a light chain (LC), or is substantially composed of, or is composed of, the HC includes SEQ ID NO:26 amino acid sequence or its equivalent, or is substantially composed of, or is composed of, the LC includes SEQ ID NO:27 amino acid sequence or its equivalent, or is substantially composed of, or is composed of. In another embodiment, the antibody or fragment thereof is bound to the tail region of DNABII peptide (including but not limited to the tail region of IHF or HU, the tail region of IHFA or IHFB and / or tail chimeric peptide IhfA3-IhfB2 NTHI In one embodiment, the antibody or fragment thereof binds to the tail chimeric peptide IhfA3-IhfB2 NTHI. In another embodiment, the fragment is an antigen-binding fragment. In one embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) and / or a light chain (LC), the HC comprising the amino acid sequence of SEQ ID NO: 4 or an equivalent thereof, or consisting essentially of, or consisting of, the LC comprising the amino acid sequence of SEQ ID NO: 10 or an equivalent thereof, or consisting essentially of, or consisting of. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) and / or a light chain (LC), the HC comprising the amino acid sequence of SEQ ID NO: 4 or an equivalent thereof, or consisting essentially of, or consisting of, the LC comprising the amino acid sequence of SEQ ID NO: 11 or an equivalent thereof, or consisting essentially of, or consisting of. In one embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 4 or an equivalent thereof, and / or a light chain (LC) comprising, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 12 or an equivalent thereof. In one embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 5 or an equivalent thereof, and / or a light chain (LC) comprising, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 10 or an equivalent thereof. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) and / or a light chain (LC), wherein the HC comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 5 or an equivalent thereof, and the LC comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 11 or an equivalent thereof. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) and / or a light chain (LC), wherein the HC comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 5 or an equivalent thereof, and the LC comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 12 or an equivalent thereof. In one embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) and / or a light chain (LC), wherein the HC comprises the amino acid sequence of SEQ ID NO: 6 or an equivalent thereof, or consists essentially of, or consists of, and the LC comprises the amino acid sequence of SEQ ID NO: 10 or an equivalent thereof, or consists essentially of, or consists of.In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 6 or an equivalent thereof, and / or a light chain (LC) comprising, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 11 or an equivalent thereof. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 6 or an equivalent thereof, and / or a light chain (LC) comprising, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 12 or an equivalent thereof.

[0221] In yet another aspect, there is provided herein an antibody or its fragment, it comprises heavy chain (HC) and / or light chain (LC), or is substantially composed of it, or is composed of it, the HC comprises SEQ ID NO:24 aa 25 to aa 473 amino acid sequence or its equivalent, or is substantially composed of it, or is composed of it, the LC comprises SEQ ID NO:25 aa 21 to aa 239 amino acid sequence or its equivalent, or is substantially composed of it, or is composed of it. In another embodiment, the antibody or its fragment is attached to the head region of DNABII peptide (including but not limited to the head region of IHF or HU, the head region of IHFA or IHFB and / or head chimeric peptide IhfA5-mIhfB4 NTHI In one embodiment, the antibody or fragment thereof binds to the head chimeric peptide IhfA5-mIhfB4 NTHI. In another embodiment, the fragment is an antigen-binding fragment. In one embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) and / or a light chain (LC), wherein the HC comprises the amino acid sequence of aa 25 to aa 473 of SEQ ID NO: 1, or an equivalent thereof, or consists essentially of, or consists of, and the LC comprises the amino acid sequence of aa 21 to aa 239 of SEQ ID NO: 7, or an equivalent thereof, or consists essentially of, or consists of. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) and / or a light chain (LC), wherein the HC comprises the amino acid sequence of aa 25 to aa 473 of SEQ ID NO: 1, or an equivalent thereof, or consists essentially of, or consists of, and the LC comprises the amino acid sequence of aa 21 to aa 239 of SEQ ID NO: 8, or an equivalent thereof, or consists essentially of, or consists of. In one embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising, consists essentially of, or consists of an amino acid sequence of aa 25 to aa 473 of SEQ ID NO: 1, or an equivalent thereof, and / or a light chain (LC) comprising, consists essentially of, or consists of an amino acid sequence of aa 21 to aa 239 of SEQ ID NO: 9, or an equivalent thereof. In one embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising, consists essentially of, or consists of an amino acid sequence of aa 25 to aa 473 of SEQ ID NO: 2, or an equivalent thereof, and / or a light chain (LC) comprising, consists essentially of, or consists of an amino acid sequence of aa 21 to aa 239 of SEQ ID NO: 7, or an equivalent thereof. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising the amino acid sequence of aa25 to aa 473 of SEQ ID NO:2, or an equivalent thereof, or consists essentially of, or consists of, and / or a light chain (LC) comprising, consists essentially of, or consists of, the amino acid sequence of aa 21 to aa 239 of SEQ ID NO:8, or an equivalent thereof.In one embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising, consists essentially of, or consists of an amino acid sequence of aa 25 to aa 473 of SEQ ID NO: 1, or an equivalent thereof, and / or a light chain (LC) comprising, consists essentially of, or consists of an amino acid sequence of aa 21 to aa 239 of SEQ ID NO: 9, or an equivalent thereof. In one embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising, consists essentially of, or consists of an amino acid sequence of aa 25 to aa 473 of SEQ ID NO: 3, or an equivalent thereof, and / or a light chain (LC) comprising, consists essentially of, or consists of an amino acid sequence of aa 21 to aa 239 of SEQ ID NO: 7, or an equivalent thereof. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising, consists essentially of, or consists of the amino acid sequence of aa 25 to aa 473 of SEQ ID NO: 3, or an equivalent thereof, and / or a light chain (LC) comprising, consists essentially of, or consists of the amino acid sequence of aa 21 to aa 239 of SEQ ID NO: 8, or an equivalent thereof. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising, consists essentially of, or consists of the amino acid sequence of aa 25 to aa 473 of SEQ ID NO: 3, or an equivalent thereof, and / or a light chain (LC) comprising, consists essentially of, or consists of the amino acid sequence of aa 21 to aa 239 of SEQ ID NO: 9, or an equivalent thereof.

[0222] In yet another aspect, there is provided herein an antibody or its fragment, it comprises heavy chain (HC) and light chain (LC), or is substantially composed of it, or is composed of it, the HC comprises SEQ ID NO:26 aa 25 to aa 473 amino acid sequence or its equivalent, or is substantially composed of it, or is composed of it, the LC comprises SEQ ID NO:27 aa 21 to aa 233 amino acid sequence or its equivalent, or is substantially composed of it, or is composed of it. In another embodiment, the antibody or its fragment is attached to the tail region of DNABII peptide (including but not limited to the tail region of IHF or HU, the tail region of IHFA or IHFB and / or tail chimeric peptide IhfA3-IhfB2 NTHI In one embodiment, the antibody or fragment thereof binds to the tail chimeric peptide IhfA3-IhfB2 NTHIIn another embodiment, the fragment is an antigen-binding fragment. In one embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising, consists essentially of, or consists of the amino acid sequence of aa25 to aa 473 of SEQ ID NO: 4, or an equivalent thereof, and / or a light chain (LC) comprising, consists essentially of, or consists of the amino acid sequence of aa 21 to aa 233 of SEQ ID NO: 10, or an equivalent thereof. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising, consists essentially of, or consists of an amino acid sequence of aa 25 to aa 473 of SEQ ID NO: 4, or an equivalent thereof, and / or a light chain (LC) comprising, consists essentially of, or consists of an amino acid sequence of aa 21 to aa 233 of SEQ ID NO: 11, or an equivalent thereof. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising, consists essentially of, or consists of an amino acid sequence of aa 25 to aa 473 of SEQ ID NO: 4, or an equivalent thereof, and / or a light chain (LC) comprising, consists essentially of, or consists of an amino acid sequence of aa 21 to aa 233 of SEQ ID NO: 12, or an equivalent thereof. In one embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising, consists essentially of, or consists of an amino acid sequence of aa 25 to aa 473 of SEQ ID NO: 5, or an equivalent thereof, and / or a light chain (LC) comprising, consists essentially of, or consists of an amino acid sequence of aa 21 to aa 233 of SEQ ID NO: 10, or an equivalent thereof. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising, consists essentially of, or consists of an amino acid sequence of aa 25 to aa 473 of SEQ ID NO: 5, or an equivalent thereof, and / or a light chain (LC) comprising, consists essentially of, or consists of an amino acid sequence of aa 21 to aa 233 of SEQ ID NO: 11, or an equivalent thereof.In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising, consists essentially of, or consists of an amino acid sequence of aa 25 to aa 473 of SEQ ID NO: 5, or an equivalent thereof, and / or a light chain (LC) comprising, consists essentially of, or consists of an amino acid sequence of aa 21 to aa 233 of SEQ ID NO: 12, or an equivalent thereof. In one embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising, consists essentially of, or consists of an amino acid sequence of aa 25 to aa 473 of SEQ ID NO: 6, or an equivalent thereof, and / or a light chain (LC) comprising, consists essentially of, or consists of an amino acid sequence of aa 21 to aa 233 of SEQ ID NO: 10, or an equivalent thereof. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising, consists essentially of, or consists of the amino acid sequence of aa 25 to aa 473 of SEQ ID NO: 6, or an equivalent thereof, and / or a light chain (LC) comprising, consists essentially of, or consists of the amino acid sequence of aa 21 to aa 233 of SEQ ID NO: 11, or an equivalent thereof. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) comprising, consists essentially of, or consists of the amino acid sequence of aa 25 to aa 473 of SEQ ID NO: 6, or an equivalent thereof, and / or a light chain (LC) comprising, consists essentially of, or consists of the amino acid sequence of aa 21 to aa 233 of SEQ ID NO: 12, or an equivalent thereof.

[0223] In one aspect, there is provided herein an antibody or its fragment, it includes following CDR sequence, or is substantially made up of it, or is made up of it: be selected from SEQ ID NO:1-3 or 24 or its each equivalent sequence any one, any two or all three CDR; And / or be selected from SEQ ID NO:7-9 or 25 or its each equivalent sequence any one, any two or all three CDR. In another embodiment, described antibody or its fragment combines the head region of DNABII peptide (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB and / or head chimeric peptide IhfA5-mIhfB4 NTHI In one embodiment, the antibody or fragment thereof binds to the head chimeric peptide IhfA5-mIhfB4 NTHIIn another embodiment, the fragment is an antigen-binding fragment. In one embodiment, provided herein is an antibody or fragment thereof comprising, consisting essentially of, or consisting of the following CDR sequences: all three CDRs of a sequence selected from SEQ ID NOs: 1-3 or 24, or an equivalent thereof; and / or all three CDRs of a sequence selected from SEQ ID NOs: 7-9 or 25, or an equivalent thereof.

[0224] In another embodiment, there is provided herein an antibody or its fragment, it includes following CDR sequences, or is substantially made up of it, or is made up of it: be selected from SEQ ID NO:4-6 or 26 or the sequence of its each equivalent any one, any two or all three CDR; And / or be selected from SEQ ID NO:10-12 or 27 or the sequence of its each equivalent any one, any two or all three CDR. In another embodiment, the antibody or its fragment is attached to the tail region of DNABII peptide (including but not limited to the tail region of IHF or HU, the tail region of IHFA or IHFB and / or tail chimeric peptide IhfA3-IhfB2 NTHI In one embodiment, the antibody or fragment thereof binds to the tail chimeric peptide IhfA3-IhfB2 NTHI In another embodiment, the fragment is an antigen-binding fragment. In one embodiment, provided herein is an antibody or fragment thereof comprising, consisting essentially of, or consisting of the following CDR sequences: all three CDRs of a sequence selected from SEQ ID NOs: 4-6 or 26, or an equivalent thereof; and / or all three CDRs of a sequence selected from SEQ ID NOs: 10-12 or 27, or an equivalent thereof.

[0225] In certain embodiments, the antibodies or fragments thereof provided herein further comprise one or more signal peptides. In one embodiment, the signal peptide comprises, or consists essentially of, or consists of amino acids (aa) 1 to aa 24 of any one of SEQ ID NOs: 1-6, 13, 24, or 26. In another embodiment, the signal peptide comprises, or consists essentially of, or consists of aa 1 to aa 20 of any one of SEQ ID NOs: 7-12, 14, 25, and 27. In a further embodiment, the signal peptide is located at the amino terminus of the light chain variable region. Additionally or alternatively, the same signal peptide or a different signal peptide is located at the amino terminus of the heavy chain variable region.

[0226] Antibodies provided herein or their fragments can be monospecific or bispecific. In one embodiment, the antibody or its fragment is trispecific or tetraspecific or pentaspecific. Additionally or alternatively, the antibody is selected from IgA (e.g., IgA1 or IgA2), IgD, IgE, IgG (e.g., IgG1, IgG2, IgG3, or IgG4) or IgM antibodies. In one embodiment, the antibody further comprises a constant region selected from: IgA constant region (e.g., IgA1 constant region or IgA2 constant region), IgD constant region, IgE constant region, IgG constant region (e.g., IgG1 constant region, IgG2 constant region, IgG3 constant region, or IgG4 constant region) or IgM constant region.

[0227] In certain embodiments, an equivalent of an amino acid sequence comprises, consists essentially of, or consists of a polypeptide having at least about 80% (including about 80% to 100%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99%) amino acid identity with the amino acid sequence. Additionally or alternatively, an equivalent of an amino acid sequence comprises, consists essentially of, or consists of a polypeptide encoded by a polynucleotide that hybridizes under high stringency to the complement of a polynucleotide encoding the amino acid sequence. In further embodiments, equivalents of an amino acid sequence comprise, consist essentially of, or consist of a polypeptide having at least about 80% (including about 80% to 100%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99%) amino acid identity with the amino acid sequence. In certain embodiments, an equivalent of an amino acid sequence (e.g., an antibody or fragment thereof, or any one or more of SEQ ID NOs: 1-14 and 24-26 as disclosed herein, or fragments thereof, including but not limited to aa 25 to aa 144 of SEQ ID NO: 13, 24 or 26, aa 21 to aa 132 of SEQ ID NO: 14 or 25, aa 21 to aa 126 of SEQ ID NO: 27, aa 25 to aa 473 of SEQ ID NO: 13, 24 or 26, aa 21 to aa 239 of SEQ ID NO: 14 or 25, aa21 to aa 233 of SEQ ID NO: 27) comprises, consists essentially of, or consists of a polypeptide comprising one or more or all of the CDRs of the amino acid sequence. Additionally or alternatively, the polypeptide has at least about 80% (including about 80% to 100%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99%) amino acid identity with the amino acid sequence.

[0228] In certain embodiments, an equivalent of an amino acid sequence (e.g., an antibody, fragment thereof, complementarity determining region (CDR) thereof, or a CDR-containing polypeptide) lacks amino acid differences in the CDRs of the amino acid sequence. However, an equivalent of an amino acid sequence (e.g., an antibody, fragment thereof, complementarity determining region (CDR) thereof, or a CDR-containing polypeptide) may comprise one or more amino acid differences in the non-CDR regions compared to the amino acid sequence, such as, but not limited to, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 amino acid differences, provided that the three-dimensional arrangement of the CDRs and / or the CDRs are maintained. In certain embodiments, an equivalent polypeptide of an amino acid sequence (e.g., an antibody, fragment thereof, complementarity determining region (CDR) thereof, or a CDR-containing polypeptide) has at least about 80% (including about 80% to 100%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99%) amino acid identity with the amino acid sequence, provided that the three-dimensional arrangement of the CDRs and / or the CDRs are maintained.

[0229] Non-limiting examples of such non-CDR regions include framework regions (FRs), constant regions, Fc regions, pFc' regions, heavy chain (CH) constant domains (e.g., CH1, CH2, CH3, or CH4), light chain (CL) constant domains, or hinge regions. In one embodiment, such amino acid differences may be conservative amino acid substitutions and / or do not alter the three-dimensional arrangement of the antibody, its fragment, its CDR, or CDR-containing polypeptide. In another embodiment, equivalents may comprise conservative amino acid substitutions at the boundaries of the CDRs, such as one or two amino acids at the amino terminus, carboxyl terminus, or both of the CDRs.

[0230] In one aspect, provided herein are one or more CDRs (e.g., any 1, or 2, or 3, or 4, or 5, or 6 CDRs) of an antibody or fragment thereof as disclosed herein. In one embodiment, provided herein are a set of CDRs comprising, consisting essentially of, or consisting of one or more CDRs (e.g., any 1, or 2, or 3, or 4, or 5, or 6 CDRs) of an antibody or fragment thereof as disclosed herein. In one embodiment, provided herein are a set of CDRs comprising, consisting essentially of, or consisting of CDRL1, CDRL2, and CDRL3 of a variable region as disclosed herein. In another embodiment, provided herein are a set of CDRs comprising, consisting essentially of, or consisting of CDRH1, CDRH2, and CDRH3 of a variable region as disclosed herein. In another embodiment, a group of CDRs is provided, which comprise CDRL1, CDRL2 and CDRL3 of a variable region as disclosed herein and CDRH1, CDRH2 and CDRH3 of another variable region as disclosed herein, or are substantially composed of, or are composed of. In certain embodiments, the CDR group constitutes a paratope. Additionally or alternatively, the group of CDRs specifically binds to DNABII peptides (e.g., head region and / or tail region, including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB, the head chimeric peptide IhfA5-mIhfB4 NTHI , the tail region of IHF or HU, the tail region of IHFA or IHFB, and / or the tail chimeric peptide IhfA3-IhfB2 NTHI In another embodiment, an antibody, fragment thereof, or their respective equivalents is provided, comprising, consisting essentially of, or consisting of any one or more CDRs as disclosed herein. In yet another embodiment, an antibody, fragment thereof, or their respective equivalents is provided, comprising, consisting essentially of, or consisting of a CDR set as disclosed herein.

[0231] In certain embodiments, the CDRs of SEQ ID NOs: 1-13 are described in the table below. In certain embodiments, the CDRH1 of any one of SEQ ID NOs: 1-6, 13, 24, or 26 comprises, consists essentially of, or consists of amino acids (aa) 50 to aa 57 of SEQ ID NOs: 1-6, 13, 24, or 26, respectively. In certain embodiments, the CDRH2 of any one of SEQ ID NOs: 1-6, 13, 24, or 26 comprises, consists essentially of, or consists of amino acids (aa) 75 to aa 82 of SEQ ID NOs: 1-6, 13, 24, or 26, respectively. In certain embodiments, the CDRH3 of any one of SEQ ID NOs: 1-6, 13, 24, or 26 comprises, consists essentially of, or consists of amino acids (aa) 121 to aa 133 of SEQ ID NOs: 1-6, 13, 24, or 26, respectively. In certain embodiments, the CDRL1 of any one of SEQ ID NOs: 7-9, 14, or 25 comprises, consists essentially of, or consists of amino acids (aa) 47 to aa 57 of SEQ ID NOs: 7-9, 14, or 25, respectively. In certain embodiments, the CDRL2 of any one of SEQ ID NOs: 7-9, 14, or 25 comprises, consists essentially of, or consists of amino acids (aa) 75 to aa 77 of SEQ ID NOs: 7-9, 14, or 25, respectively. In certain embodiments, the CDRL3 of any one of SEQ ID NOs: 7-9, 14, or 25 comprises, consists essentially of, or consists of amino acids (aa) 114 to aa 122 of SEQ ID NOs: 7-9, 14, or 25, respectively. In certain embodiments,

[0232] The CDRL1 of any one of SEQ ID NOs: 10-12 or 27 comprises, consists essentially of, or consists of amino acids (aa) 47 to aa 52 of SEQ ID NOs: 10-12 or 27, respectively. In certain embodiments, the CDRL2 of any one of SEQ ID NOs: 10-12 or 27 comprises, consists essentially of, or consists of amino acids (aa) 70 to aa 72 of SEQ ID NOs: 10-12 or 27, respectively. In certain embodiments, the CDRL3 of any one of SEQ ID NOs: 10-12 or 27 comprises, consists essentially of, or consists of amino acids (aa) 109 to aa 116 of SEQ ID NOs: 10-12 or 27, respectively.

[0233]

[0234]

[0235] In certain embodiments, the CDRs are provided in the following two tables.

[0236]

[0237]

[0238]

[0239] SEQ:SEQ ID NO

[0240]

[0241]

[0242]

[0243] SEQ:SEQ ID NO

[0244] In certain embodiments, another CDR is provided that is a CDR as identified herein and further comprises an additional 1 amino acid, or 2 amino acids, or 3 amino acids, or 4 amino acids, or 5 amino acids, or 6 amino acids, or 7 amino acids, or 8 amino acids at its amino terminus, carboxyl terminus, or both in the corresponding variable region sequence. Additionally or alternatively, another CDR is provided that is a CDR as identified herein and truncated at its amino terminus, carboxyl terminus, or both in the corresponding variable region sequence by 1 amino acid, or 2 amino acids, or 3 amino acids, or 4 amino acids, or 5 amino acids, or 6 amino acids, or 7 amino acids, or 8 amino acids. For example, the CDR1 of SEQ ID NO: 1 can be amino acid 50 to amino acid 57 of SEQ ID NO: 1. However, the CDR1 of SEQ ID NO: 1 may also begin at amino acid 42, or 43, or 44, or 45, or 46, or 47, or 48, or 49, or 50, or 51, or 52, or 53, or 54, or 55, or 56, or 57, or 58 of SEQ ID NO: 1. Furthermore, the CDR1 of SEQ ID NO: 1 may end at amino acid 49, or 50, or 51, or 52, or 53, or 54, or 55, or 56, or 57, or 58, or 59, or 60, or 61, or 62, or 63, or 64, or 65 of SEQ ID NO: 1, provided that the CDR1 ends after its beginning. Additionally or alternatively, the CDRs are about 1, or about 2, or about 3, or about 4, or about 5, or about 6, or about 7, or about 8, or about 9, or about 10, or about 11, or about 12, or about 13, or about 14, or about 15 amino acids in length.

[0245] In certain embodiments, the CDR2 of any one of SEQ ID NO: 1-6 comprises, or consists essentially of, or consists of amino acid 71 to amino acid 85 of each of SEQ ID NO: 1-6, respectively. In certain embodiments, the CDR3 of any one of SEQ ID NO: 1-6 comprises, or consists essentially of, or consists of amino acid 121 to amino acid 133 of each of SEQ ID NO: 1-6, respectively. In certain embodiments, the CDR2 of any one of SEQ ID NO: 7-9 comprises, or consists essentially of, or consists of amino acid 71 to amino acid 81 of each of SEQ ID NO: 7-9, respectively. In certain embodiments, the CDR3 of any one of SEQ ID NO: 7-9 comprises, or consists essentially of, or consists of amino acid 114 to amino acid 121 of each of SEQ ID NO: 7-9, respectively. In certain embodiments, the CDR2 of any one of SEQ ID NOs: 10-12 comprises, consists essentially of, or consists of amino acids 66 to 76 of each of SEQ ID NOs: 10-12, respectively. In certain embodiments, the CDR3 of any one of SEQ ID NOs: 10-12 comprises, consists essentially of, or consists of amino acids 109 to 115 of each of SEQ ID NOs: 10-12, respectively.

[0246] In certain embodiments, the CDR1 of any one of SEQ ID NO:1-6 comprises amino acid 50 to amino acid 57 of each of SEQ ID NO:1-6, respectively, or consists essentially of it, or consists of it. In certain embodiments, the CDR2 of any one of SEQ ID NO:1-6 comprises amino acid 75 to amino acid 82 of each of SEQ ID NO:1-6, respectively, or consists essentially of it, or consists of it. In certain embodiments, the CDR3 of any one of SEQ ID NO:1-6 comprises amino acid 121 and amino acid 122 of each of SEQ ID NO:1-6, respectively, or consists essentially of it, or consists of it. In certain embodiments, the CDR1 of any one of SEQ ID NO:7-9 comprises amino acid 47 to amino acid 57 of each of SEQ ID NO:7-9, respectively, or consists essentially of it, or consists of it. In certain embodiments, the CDR2 of any one of SEQ ID NOs: 7-9 comprises, or consists essentially of, or consists of amino acids 75 to 77 of each of SEQ ID NOs: 7-9, respectively. In certain embodiments, the CDR3 of any one of SEQ ID NOs: 7-9 comprises, or consists essentially of, or consists of amino acids 114 to 120 of each of SEQ ID NOs: 7-9, respectively. In certain embodiments, the CDR1 of any one of SEQ ID NOs: 10-12 comprises, or consists essentially of, or consists of amino acids 47 to 52 of each of SEQ ID NOs: 10-12, respectively. In certain embodiments, the CDR2 of any one of SEQ ID NOs: 10-12 comprises, or consists essentially of, or consists of amino acids 70 to 72 of each of SEQ ID NOs: 10-12, respectively. In certain embodiments, the CDR3 of any one of SEQ ID NOs: 10-12 comprises, consists essentially of, or consists of amino acid 109 and amino acid 110 of each of SEQ ID NOs: 10-12, respectively.

[0247] In certain embodiments, the CDR1 of any one of SEQ ID NO:1-6 comprises, or consists essentially of, or consists of, amino acid 47 to amino acid 59 of each of SEQ ID NO:1-6, respectively. In certain embodiments, the CDR2 of any one of SEQ ID NO:1-6 comprises, or consists essentially of, or consists of, amino acid 74 to amino acid 83 of each of SEQ ID NO:1-6, respectively. In certain embodiments, the CDR1 of any one of SEQ ID NO:7-9 comprises, or consists essentially of, or consists of, amino acid 44 to amino acid 59 of each of SEQ ID NO:7-9, respectively. In certain embodiments, the CDR2 of any one of SEQ ID NO:7-9 comprises, or consists essentially of, or consists of, amino acid 74 to amino acid 81 of each of SEQ ID NO:7-9, respectively. In certain embodiments, the CDR3 of any one of SEQ ID NOs: 7-9 comprises, consists essentially of, or consists of amino acid 114 to amino acid 122 of each of SEQ ID NOs: 7-9, respectively. In certain embodiments, the CDR1 of any one of SEQ ID NOs: 10-12 comprises, consists essentially of, or consists of amino acid 44 to amino acid 54 of each of SEQ ID NOs: 10-12, respectively. In certain embodiments, the CDR2 of any one of SEQ ID NOs: 10-12 comprises, consists essentially of, or consists of amino acid 79 to amino acid 76 of each of SEQ ID NOs: 10-12, respectively. In certain embodiments, the CDR3 of any one of SEQ ID NOs: 10-12 comprises, consists essentially of, or consists of amino acid 109 to amino acid 116 of each of SEQ ID NOs: 10-12, respectively.

[0248] On the one hand, one or more variable regions of an antibody as disclosed herein or its fragment, and / or one or more equivalents of variable region are provided. In a further embodiment, a kind of antibody, its fragment or their respective equivalent is provided, it comprises following any one or any two or more components, or is substantially made up of it, or is made up of it: variable region as disclosed herein and / or one or more equivalents of variable region. In addition or as an alternative, these one or more variable region specific binding DNABII peptide (such as head region and / or tail region, including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB, head chimeric peptide IhfA5-mIhfB4 NTHI , the tail region of IHF or HU, the tail region of IHFA or IHFB, and / or the tail chimeric peptide IhfA3-IhfB2 NTHIIn certain embodiments, the variable region is selected from the group consisting of: amino acid (aa) 25 to aa 144 of SEQ ID NOs: 1-6, 13, 24, and 26; aa 21 to aa 132 of SEQ ID NOs: 7-9, 14, and 25; aa 21 to aa 126 of SEQ ID NOs: 10-12 or 27; amino acid 24 to amino acid 144 of SEQ ID NOs: 1-6, 13, 24, and 26; amino acid 20 to amino acid 132 of SEQ ID NOs: 7-12, 14, 25, and 27; and amino acid 20 to amino acid 126 of SEQ ID NOs: 7-12, 14, 25, and 27.

[0249] In a further embodiment, the variable region or its equivalent is a variable region as disclosed herein and further comprises an additional 1 amino acid, or 2 amino acids, or 3 amino acids, or 4 amino acids, or 5 amino acids, or 6 amino acids, or 7 amino acids, or 8 amino acids at the amino terminus, or carboxyl terminus, or both, of the corresponding sequence provided herein as SEQ ID NO. Additionally or alternatively, the variable region or its equivalent is a variable region as disclosed herein and truncated at the amino terminus, or carboxyl terminus, or both, of the corresponding sequence provided herein as SEQ ID NO. For example, SEQ ID

[0250] The variable region of SEQ ID NO: 1 may be amino acid 50 to amino acid 57 of SEQ ID NO: 1. However, the variable region related to the variable region consisting of amino acid 24 to amino acid 144 of SEQ ID NO: 1, or its equivalent, may also start at amino acid 16, or 17, or 18, or 19, or 20, or 21, or 22, or 23, or 24, or 25, or 26, or 27, or 28, or 29, or 30, or 31, or 32 of SEQ ID NO: 1. Further, a variable region related to the variable region consisting of amino acid 24 to amino acid 144 of SEQ ID NO: 1, or its equivalent, may also end at amino acid 136, or 137, or 138, or 139, or 140, or 141, or 142, or 143, or 144, or 145, or 146, or 147, or 148, or 149, or 150, or 151, or 152 of SEQ ID NO: 1, provided that the variable region ends after it begins. Additionally or alternatively, the variable region is about 90 amino acids long to about 200 amino acids long, e.g., about 100 amino acids long, or about 110 amino acids long, or about 120 amino acids long, or about 130 amino acids long, or about 140 amino acids long, or about 150 amino acids long, or about 160 amino acids long, or about 170 amino acids long, or about 180 amino acids long, or about 190 amino acids long, or about 200 amino acids long.

[0251] In addition or as an alternative, an equivalent of an antibody or fragment thereof comprises one or more (for example, but not limited to, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25) amino acid differences compared to the antibody or fragment thereof in regions outside the variable domain (referred to herein as non-VH regions). Such non-VH regions include, but are not limited to, constant regions, Fc regions, pFc' regions, heavy chain constant (CH) domains (e.g., CH1, CH2, CH3, or CH4), light chain constant (CL) domains, or hinge regions. Those skilled in the art will appreciate that the antibodies, fragments thereof, or their respective equivalents disclosed herein can be further modified in non-VH regions (e.g., to increase assembly of heavy and light chains, to conjugate directly or indirectly to a detectable or purification marker or drug, to increase or decrease complement activation, to enhance or decrease antibody-dependent cellular cytotoxicity (ADCC), or to increase or decrease activation and recruitment of immune cells), thereby providing further equivalents.

[0252] In certain embodiments, the equivalent further comprises up to 50, or up to 30, or up to 25, or up to 20, or up to 15, or up to 10, or up to 5 random amino acids at the amino terminus, or the carboxyl terminus, or both. In certain embodiments, the equivalent of an amino acid sequence comprises, consists essentially of, or consists of an amino acid sequence truncated at the amino terminus, or the carboxyl terminus, or both, for example, by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, or 25 amino acids. Such additions or truncations may not alter the three-dimensional arrangement of the CDRs and / or the three-dimensional arrangement of the antibody, fragment thereof, CDRs thereof, or CDR-containing polypeptide.

[0253] In certain embodiments, the antibody or fragment thereof comprises a signal peptide at the amino terminus of VH and / or the amino terminus of VL. In one embodiment, the VH signal peptide is different from the VL signal peptide. In another embodiment, the VL signal peptide and the VH signal peptide are the same. In another embodiment, the signal peptide comprises, consists essentially of, or consists of an amino acid sequence of amino acids 1-24 of SEQ ID NO: 1. In yet another embodiment, the signal peptide comprises, consists essentially of, or consists of an amino acid sequence of amino acids 1-20 of SEQ ID NO: 7. In certain embodiments, an equivalent of an antibody or fragment thereof comprises a signal peptide that is different from the signal peptide of the antibody, provided that the signal peptide of the equivalent directs VH and / or VL to the same cellular location as the signal peptide of the antibody.

[0254] In certain embodiments, the equivalent of antibody or its fragment retains at least 50% (for example at least 60%, at least 70%, at least 80%, at least 90%, at least 95% or at least 99%) or improves one or more functional activities of the antibody or fragment. Such functional activities include but are not limited to DNABII peptide (for example head region and / or tail region, including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB, the head chimeric peptide IhfA5-mIhfB4 NTHI , the tail region of IHF or HU, the tail region of IHFA or IHFB, and / or the tail chimeric peptide IhfA3-IhfB2 NTHI ) to prevent the formation of biofilms in vivo or in vitro, or to disrupt biofilms in vivo or in vitro. Methods for quantifying such functional activities are described in the Examples.

[0255] In another aspect, an antibody or fragment thereof that competes with an antibody or fragment thereof disclosed herein for binding to an epitope is provided. The antibody or fragment thereof can be a polyclonal, monoclonal and / or humanized antibody.

[0256] In one aspect, the antibody is a bispecific antibody or a trispecific, tetraspecific or pentaspecific antibody. In another aspect, the antibody is an IgA, IgD, IgE, IgG or IgM antibody. In another aspect, the antibody further comprises a constant region selected from an IgA, IgD, IgE, IgG or IgM constant region. In a specific aspect, the constant region is an IgG1 constant region. In another aspect, provided herein are antibodies that compete with the antibody disclosed herein for binding epitopes. These can be identified using conventional techniques (e.g., competitive ELISA).

[0257] Antibodies as disclosed herein can be polyclonal, monoclonal or humanized. On the one hand, antibody binds to " head " region of DNABII polypeptide (such as HU or IHF (such as IhfA and IhfB)). On the other hand, antibody binds to " tail " region of DNABII polypeptide (such as HU or IHF (such as IhfA and IhfB)). As mentioned above, the disclosure provides antigen binding fragments. Antigen binding fragments are any one of Fab, F (ab') 2, Fab', scFv or Fv, which can be prepared using conventional techniques known to those skilled in the art. In some aspects of the antibody provided herein, the antibody is a soluble Fab. In another aspect, the disclosure provides the Fab fragment of an antibody as disclosed herein, wherein the antibody specifically binds to the head region of DNABII peptide (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB, and / or head chimeric peptide IhfA5-mIhfB4 NTHI ). In one aspect of the present disclosure, DNABII is an IHF or HU peptide. In a specific aspect, DNABII is an IHF peptide.

[0258] As described above, the present disclosure provides equivalents of antibodies and antigen-binding fragments. Equivalents may comprise polypeptides having at least 80% amino acid identity with the polypeptide, or polypeptides encoded by polynucleotides that hybridize under highly stringent conditions to the complement of a polynucleotide encoding the polypeptide.

[0259] In some aspects of the antibodies provided herein, the antibody, fragment, polypeptide or CDR thereof is administered at a half maximal effective concentration (EC) of less than 500 ng / mL, or less than 250 ng / mL, or less than 200 ng / mL, or less than 150 ng / mL, or less than 100 ng / mL, or less than 90 ng / mL, or less than 80 ng / mL, or less than 70 ng / mL, or less than 65 ng / mL, or less than 60 ng / mL, or less than 55 ng / mL, or less than 50 ng / mL, or less than 45 ng / mL, or less than 40 ng / mL, or less than 35 ng / mL, or less than 30 ng / mL. 50) binds to DNABII protein (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB, the head chimeric peptide IhfA5-mIhfB4 NTHI , the tail region of IHF or HU, the tail region of IHFA or IHFB, and / or the tail chimeric peptide IhfA3-IhfB2 NTHI In a further embodiment, the ELISA method shown in the examples is used to determine such EC 50 .

[0260] In some aspects of the antibodies provided herein, the antibody, fragment, polypeptide, or CDR thereof is expressed in less than 10 -4 M, 10 -5 M, 10 - 6 M, 10 -7 M, 10 -8 M, 10 -9 M, 10 -10 M, 10 -11 M or 10 -12 The equilibrium constant K of M D Binds to DNABII protein (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB, the head chimeric peptide IhfA5-mIhfB4 NTHI , the tail region of IHF or HU, the tail region of IHFA or IHFB, and / or the tail chimeric peptide IhfA3-IhfB2 NTHI In one embodiment, the antibody, fragment, polypeptide or CDR thereof is as follows: D Binding to DNABII protein: less than 1000nM, or less than 900nM, or less than 800nM, or less than 700nM, or less than 600nM, or less than 500nM, or less than 400nM, or less than 300nM, or less than 200nM, or less than 100nM, or less than 90nM, or less than 80nM, or less than 70nM, or less than 60nM, or less than 50nM, or less than 40nM, or less than 30nM, or less than 20nM, or less than 15nM, or less than 10nM, or less than 9nM, or less than 8nM, or less than 7nM, or less than 6nM, or less than 5nM, or less than 4nM, or less than 3nM, or less than 2nM, or less than 1nM. In one embodiment, this K D This was determined using the surface plasmon resonance (SPR) method shown in the Examples. In some aspects of the antibodies provided herein, the antigen binding site specifically binds to DNABII protein.

[0261] In some aspects of the antibodies provided herein, the antibody, fragment, polypeptide, or CDR thereof is as follows:off Binds to DNABII protein (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB, the head chimeric peptide IhfA5-mIhfB4 NTHI , the tail region of IHF or HU, the tail region of IHFA or IHFB, and / or the tail chimeric peptide IhfA3-IhfB2 NTHI ): less than 1.0E-02s -1 , or less than 9.0E-03s -1 , or less than 8.0E-03s -1 , or less than 7.0E-03s -1 , or less than 6.0E-03s -1 , or less than 5.0E-03s -1 , or less than 4.0E-03s -1 , or less than 3.0E-03s -1 , or less than 2.0E-03s -1 , or less than 1.0E-03s -1 , or less than 9.0E-04s -1 , or less than 8.0E-04s -1 , or less than 7.0E-04s -1 , or less than 6.0E-04s -1 , or less than 5.0E-04s -1 , or less than 4.0E-04s -1 , or less than 3.0E-04s -1 , or less than 2.0E-04s -1 , or less than 1.0E-04s -1 , or less than 9.0E-05s -1 , or less than 8.0E-05s -1 , or less than 7.0E-05s -1 , or less than 6.0E-05s -1 , or less than 5.0E-05s -1 , or less than 4.0E-05s -1 , or less than 3.0E-05s -1 , or less than 2.0E-05s -1 , or less than 1.0E-05s -1 In one embodiment, this K off It was determined using the surface plasmon resonance (SPR) method shown in the Examples.

[0262] In some aspects of the antibodies provided herein, the antibody, fragment, polypeptide, or CDR thereof is as follows: onBinds to DNABII protein (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB, the head chimeric peptide IhfA5-mIhfB4 NTHI , the tail region of IHF or HU, the tail region of IHFA or IHFB, and / or the tail chimeric peptide IhfA3-IhfB2 NTHI ): less than 9.0E-02M -1 s -1 , or less than 8.0E-02M -1 s -1 , or less than 7.0E-02M -1 s -1 , or less than 6.0E-02M -1 s -1 , or less than 5.0E-02M -1 s -1 , or less than 4.0E-02M -1 s -1 , or less than 3.0E-02M -1 s -1 , or less than 2.0E-02M -1 s -1 , or less than 1.0E-02M -1 s -1 , or less than 9.0E-03M -1 s -1 , or less than 8.0E-03M -1 s -1 , or less than 7.0E-03M -1 s -1 , or less than 6.0E-03M -1 s -1 , or less than 5.0E-03M -1 s -1 , or less than 4.0E-03M -1 s -1 , or less than 3.0E-03M -1 s -1 , or less than 2.0E-03M -1 s -1 , or less than 1.0E-03M -1 s -1 , or less than 9.0E-04M -1 s -1 , or less than 8.0E-04M -1 s -1 , or less than 7.0E-04M -1 s -1 , or less than 6.0E-04M -1 s -1, or less than 5.0E-04M -1 s -1 , or less than 4.0E-04M -1 s -1 , or less than 3.0E-04M -1 s -1 , or less than 2.0E-04M -1 s -1 , or less than 1.0E-04M -1 s -1 , or below 9.0E-05M -1 s -1 , or less than 8.0E-05M -1 s -1 , or less than 7.0E-05M -1 s -1 , or less than 6.0E-05M -1 s -1 , or less than 5.0E-05M -1 s -1 , or less than 4.0E-05M -1 s -1 , or less than 3.0E-05M -1 s -1 , or less than 2.0E-05M -1 s -1 , or less than 1.0E-05M -1 s -1 In one embodiment, this K on It was determined using the surface plasmon resonance (SPR) method shown in the Examples.

[0263] In some aspects of the invention, IhfA5-mIhfB4 NTHI Association constant K of the head chimeric peptide A (1 / M) is about 3E+05 to about 2E+08. On the other hand, K A From about 3E+05 to about 1E+08, or about 2E+05 to about 1E+08, or about 1E+05 to about 1E+08, or about 1E+06 to about 1E+08, or about 1E+07 to about 1E+08, or about 1E+04 to about 1E+09, or about 1E+05 to about 1E+09, or about 1E+06 to about 1E+09, or about 1E+07 to about 1E+09, or about 1E+08 to about 1E+09, or about 1E+04 to about 1E+09, or about 1E+03 to about 1E+10.

[0264] In another aspect, IhfA5-mIhfB4 NTHI Dissociation constant K of the head chimeric peptide D(M) is from about 5E-09 to about 3E-06, or from about 1E-09 to about 1E-06, or from about 1E-08 to about 1E-05, or from about 1E-07 to about 1E-05, or from about 1E-06 to about 1E-05, or from about 1E-09 to about 1E-08, or from about 1E-08 to about 1E-07, or from about 1E-9 to about 1E-08, or from about 1E-10 to about 1E-09, or from about 1E-11 to about 1E-10.

[0265] In one aspect, IhfA3-IhfB2 NTHI K of the tail chimeric peptide A (I / M) is from about 7E+06 to about 2E+09, or from about 1E+05 to about 1E+08, or from about 1E+06 to about 1E+08, or from about 1E+07 to about 1E+08, or from about 1E+04 to about 1E+09, or from about 1E+05 to about 1E+09, or from about 1E+06 to about 1E+09, or from about 1E+07 to about 1E+09, or from about 1E+08 to about 1E+09, or from about 1E+04 to about 1E+09, or from about 1E+03 to about 1E+10, or from about 1E+03 to about 1E+11, or from about 1E+03 to about 1E+12, or from about 1E+09 to about 1E+10, or from about 1E+10 to about 1E+11, or from about 1E+11 to about 1E+12.

[0266] In another aspect, IhfA3-IhfB2 NTHI K of the tail chimeric peptide D (M) is from about 6E-10 to about 2E-07, or from about 1E-09 to about 1E-06, or from about 1E-08 to about 1E-05, or from about 1E-07 to about 1E-05, or from about 1E-06 to about 1E-05, or from about 1E-09 to about 1E-08, or from about 1E-08 to about 1E-07, or from about 1E-9 to about 1E-08, or from about 1E-10 to about 1E-09, or from about 1E-11 to about 1E-10, or from about 1E-11 to about 1E-12.

[0267] In some aspects of the antibodies provided herein, the head region of the DNABII protein (including but not limited to the head region of IHF or HU, the head region of IHFA or IHFB, the head chimeric peptide IhfA5-mIhfB4) is bound to the head region of the DNABII protein. NTHI) antibody, its fragment, polypeptide or CDR reduce the biomass of biofilm in vitro at least about 10%, or at least about 15%, or at least about 20%, or at least about 25%, or at least about 30%, or at least about 35%, or at least about 40%, or at least about 45%, or at least about 50%, or at least about 55%, or at least about 60%, or at least about 65%, or at least about 70%, or at least about 75%, or at least about 80%, or at least about 85%, or at least about 90%, or at least about 95%. In some aspects of the antibody provided herein, in conjunction with the tail region of DNABII protein (including but not limited to: the tail region of IHF or HU, the tail region of IHFA or IHFB, the tail chimeric peptide IhfA3-IhfB2 NTHI ), or less than about 10%, or less than about 12%, or less than about 15%, or less than about 20%, or less than about 25%, or less than about 30%, or less than about 35%, or less than about 40%, or less than about 45%, or less than about 50%. In one embodiment, the change in biomass is determined using the method described in Example 3 or 4.

[0268] In some aspects of the antibodies provided herein, the head region of the DNABII protein (including but not limited to the head region of IHF or HU, the head region of IHFA or IHFB, the head chimeric peptide IhfA5-mIhfB4) is bound to the head region of the DNABII protein. NTHI ), or at least about 15%, or at least about 20%, or at least about 25%, or at least about 30%, or at least about 35%, or at least about 40%, or at least about 45%, or at least about 50%, or at least about 55%, or at least about 60%, or at least about 65%, or at least about 70%, or at least about 75%, or at least about 80%, or at least about 85%, or at least about 90%, or at least about 91%, or at least about 92%, or at least about 93%, or at least about 94%, or at least about 95%, or at least about 96%, or at least about 97%, or at least about 98%, or at least about 99%. In some aspects of the antibody provided herein, in conjunction with the tail region of DNABII protein (including but not limited to: the tail region of IHF or HU, the tail region of IHFA or IHFB, tail chimeric peptide IhfA3-IhfB2 NTHI), or less than about 2%, or less than about 3%, or less than about 4%, or less than about 5%, or less than about 6%, or less than about 7%, or less than about 8%, or less than about 9%, or less than about 10%, or less than about 12%, or less than about 15%, or less than about 20%, or less than about 25%, or less than about 30%, or less than about 35%, or less than about 40%, or less than about 45%, or less than about 50%. In one embodiment, such a change in bacterial load is determined using the methods described in the Examples.

[0269] In some aspects of the antibodies provided herein, the head region of the DNABII protein (including but not limited to the head region of IHF or HU, the head region of IHFA or IHFB, the head chimeric peptide IhfA5-mIhfB4) is bound to the head region of the DNABII protein. NTHI ) antibody, its fragment, polypeptide or CDR reduce the middle ear obstruction of the object suffering from otitis media (OM) by at least about 10%, or at least about 15%, or at least about 20%, or at least about 25%, or at least about 30%, or at least about 35%, or at least about 40%, or at least about 45%, or at least about 50%, or at least about 55%, or at least about 60%, or at least about 65%, or at least about 70%, or at least about 75%, or at least about 80%, or at least about 85%, or at least about 90%, or at least about 91%, or at least about 92%, or at least about 93%, or at least about 94%, or at least about 95%, or at least about 96%, or at least about 97%, or at least about 98%, or at least about 99%. In some aspects of the antibody provided herein, in conjunction with the tail region of DNABII protein (including but not limited to: the tail region of IHF or HU, the tail region of IHFA or IHFB, tail chimeric peptide IhfA3-IhfB2 NTHI ), or less than about 2%, or less than about 3%, or less than about 4%, or less than about 5%, or less than about 6%, or less than about 7%, or less than about 8%, or less than about 9%, or less than about 10%, or less than about 12%, or less than about 15%, or less than about 20%, or less than about 25%, or less than about 30%, or less than about 35%, or less than about 40%, or less than about 45%, or less than about 50% in a subject with otitis media (OM). In one embodiment, such changes in middle ear obstruction are determined in an experimental otitis media (OM) model using the methods set forth in the Examples.

[0270] In some aspects of the antibodies provided herein, the head region of the DNABII protein (including but not limited to the head region of IHF or HU, the head region of IHFA or IHFB, the head chimeric peptide IhfA5-mIhfB4) is bound to the head region of the DNABII protein. NTHI), or at least about 15%, or at least about 20%, or at least about 25%, or at least about 30%, or at least about 35%, or at least about 40%, or at least about 45%, or at least about 50%, or at least about 55%, or at least about 60%, or at least about 65%, or at least about 70%, or at least about 75%, or at least about 80%, or at least about 85%, or at least about 90%, or at least about 91%, or at least about 92%, or at least about 93%, or at least about 94%, or at least about 95%, or at least about 96%, or at least about 97%, or at least about 98%, or at least about 99%. In one embodiment, the head region of DNABII protein (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB, the head chimeric peptide IhfA5-mIhfB4 NTHI ) antibodies, fragments thereof, polypeptides or CDRs thereof that reduce the relative mucosal biofilm score and / or biomass score in subjects with mucosal biofilm (e.g., with OM) by at least about 0.5, or at least about 1, or at least about 1.5, or at least about 2, or at least about 2.5, or at least about 3, or at least about 3.5, or at least about 4. In some aspects of the antibodies provided herein, the tail region of the DNABII protein (including but not limited to: the tail region of IHF or HU, the tail region of IHFA or IHFB, the tail chimeric peptide IhfA3-IhfB2) is bound to the DNABII protein. NTHI ) antibody, its fragment, polypeptide or CDR reduce relative mucosal biofilm score and / or biomass score in the object with mucosal biofilm (for example, with OM) and be less than about 1%, or be less than about 2%, or be less than about 3%, or be less than about 4%, or be less than about 5%, or be less than about 6%, or be less than about 7%, or be less than about 8%, or be less than about 9%, or be less than about 10%, or be less than about 12%, or be less than about 15%, or be less than about 20%, or be less than about 25%, or be less than about 30%, or be less than about 35%, or be less than about 40%, or be less than about 45%, or be less than about 50%.In one embodiment, the method for such change use shown in the embodiment of middle ear obstruction is measured in experimental otitis media (OM) model.In one embodiment, in conjunction with the tail region of DNABII protein (including but not limited to: the tail region of IHF or HU, IHFA or IHFB, tail chimeric peptide IhfA3-IhfB2 NTHI), or less than about 0.1, or less than about 0.2, or less than about 0.3, or less than about 0.4, or less than about 0.5, or less than about 0.6, or less than about 0.7, or less than about 0.8, or less than about 0.9, or less than about 1, or less than about 1.5, or less than about 2, or less than about 2.5, in a subject having a mucosal biofilm (e.g., having OM). In one embodiment, such scores are determined using the methods set forth in the Examples.

[0271] In certain embodiments, the DNABII protein is HU or IHF. In further embodiments, the DNABII protein is IhfA, IhfB or both. In yet another embodiment, the antibody, its fragment, polypeptide or CDR binds to the head region or tail region of the DNABII protein (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB, the head chimeric peptide IhfA5-mIhfB4 NTHI , the tail region of IHF or HU, the tail region of IHFA or IHFB and / or the tail chimeric peptide IhfA3-IhfB2 NTHI In one embodiment, the antibody, fragment, polypeptide, or CDR thereof binds to IhfA5-mIhfB4 NTHI In another embodiment, the antibody, fragment, polypeptide or CDR thereof binds to IhfA3-IhfB2 NTHI Tail chimeric peptide.

[0272] In some aspects of the antibodies provided herein, the antibody is a soluble Fab.

[0273] In some aspects of the antibodies provided herein, the HC and LC variable domain sequences are components of the same polypeptide chain. In some aspects of the antibodies provided herein, the HC and LC variable domain sequences are components of different polypeptide chains.

[0274] In some aspects of the antibodies provided herein, the antibody is a full-length antibody.

[0275] In some aspects of the antibodies provided herein, the antibodies are chimeric or humanized.

[0276] In some aspects of the antibodies provided herein, the antibody comprises an Fc domain. In some aspects of the antibodies provided herein, the antibody is a non-human animal antibody, such as a rat, sheep, cattle, dog, cat or rabbit antibody. In some aspects of the antibodies provided herein, the antibody is a human antibody or a humanized antibody or is non-immunogenic in humans.

[0277] In some aspects of the antibodies provided herein, the antibodies comprise human antibody framework regions. Examples of framework regions that can be fused to LC and HC sequences are known in the art, and such examples are provided in SEQ ID NOs: 15-23, or equivalents of each thereof.

[0278] In other aspects, one or more amino acid residues in the CDR of the antibodies provided herein are replaced by another amino acid. In the sense of replacement within the same amino acid family, replacement can be "conservative". Naturally occurring amino acids can be divided into the following four families, and conservative replacements will occur in these families.

[0279] 1) Amino acids with basic side chains: lysine, arginine, and histidine.

[0280] 2) Amino acids with acidic side chains: aspartic acid, glutamic acid.

[0281] 3) Amino acids with uncharged polar side chains: asparagine, glutamine, serine, threonine, tyrosine.

[0282] 4) Amino acids with non-polar side chains: glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan, and cysteine.

[0283] In another aspect, one or more amino acid residues are added to or deleted from one or more CDRs of an antibody. Such additions or deletions occur at the N or C termini of the CDR or at a position within the CDR.

[0284] By altering the amino acid sequence of an antibody CDR by adding, deleting, or substituting amino acids, various effects can be achieved, such as increasing the binding affinity to the target antigen.

[0285] It should be understood that antibodies of the present disclosure comprising such altered CDR sequences still bind to DNABII protein with similar specificity and sensitivity curves as the disclosed antibodies. This can be tested by binding assays, such as ELISA or SPR.

[0286] In another aspect, the antibody is characterized as being both immunodominant and immunoprotective as determined using appropriate assays and screening methods.

[0287] In another aspect, the antibody can be modified by conventional techniques, which in one aspect can increase the half-life of the antibody, such as PEGylation, PEG mimetics, polysialylation, HESylation, or glycosylation.

[0288] Antibodies and antigen-binding fragments may also contain a detectable label or a purification tag.

[0289] Antibodies and their derivatives

[0290] The disclosure also provides the antibody for the combination and / or specific recognition and the combination of isolated polypeptides in the method disclosed herein. The antibody can be any of the various antibodies as described herein, and the limiting examples of such an antibody include polyclonal antibodies, monoclonal antibodies, chimeric antibodies, human antibodies, veneered antibodies (veneered antibody), double antibodies, humanized antibodies, antibody derivatives, recombinant humanized antibodies or their respective equivalents (such as derivatives) or fragments. On the one hand, the fragment comprises the CDR of the antibody, or is substantially composed of it, or is composed of it. On the one hand, the antibody is detectably labeled or further comprises a detectable label that is put together with it.

[0291] Also provided herein are hybridoma cell lines that produce the monoclonal antibodies disclosed herein. Further provided herein are compositions comprising, consisting essentially of, or consisting of one or more of the above embodiments. Also provided herein are polynucleotides encoding the amino acid sequences of the antibodies and fragments, as well as methods for recombinantly or chemically synthesizing the antibody polypeptides and fragments thereof. The antibody polypeptides can be produced in eukaryotic or prokaryotic cells, or by other methods known in the art and described herein.

[0292] Examples of CDR sequences include, but are not limited to, consisting essentially of, or consisting of the following: a heavy chain variable region of an antibody or fragment thereof comprises, consists essentially of, or consists of the following polypeptide: a polypeptide encoded by the following polynucleotide sequence.

[0293] Antibodies can be produced using conventional techniques known in the art and fully described in the literature. There are several methods for producing polyclonal antibodies. For example, polyclonal antibodies are usually produced by immunizing suitable mammals (such as, but not limited to, chickens, goats, guinea pigs, hamsters, horses, mice, rats and rabbits). Antigens are injected into mammals to induce B lymphocytes to produce immunoglobulins specific for the antigen. Immunoglobulins can be purified from mammalian serum.

[0294] Variations on this method include changing the adjuvant, route and site of administration, injection volume per site, and number of sites per animal to achieve optimal production and humane handling of animals. For example, adjuvants are typically used to improve or enhance the immune response to an antigen. Most adjuvants provide an injection site antigen reservoir that allows the release of antigen stores into draining lymph nodes. Other adjuvants include surfactants and immunostimulatory molecules that promote the concentration of protein antigen molecules over a large surface area. Non-limiting examples of adjuvants for producing polyclonal antibodies include Freund's adjuvant, Ribi adjuvant system, and Titermax. Polyclonal antibodies can be produced using methods known in the art, some of which are described in U.S. Patents 7,279,559; 7,119,179; 7,060,800; 6,709,659; 6,656,746; 6,322,788; 5,686,073; and 5,670,153.

[0295] Monoclonal antibodies can be produced using conventional hybridoma techniques known in the art and described in detail in the literature. For example, hybridomas are produced by fusing a suitable immortalized cell line, such as a myeloma cell line, such as, but not limited to, Sp2 / 0, Sp2 / 0-AG14, NSO, NS1, NS2, AE-1, L.5, P3X63Ag8,653, Sp2 SA3, Sp2 MAI, Sp2 SS1, Sp2 SA5, U397, MIA 144, ACT IV, MOLT4, DA-1, JURKAT, WEHI, K-562, COS, RAJI, NIH 313, HL-

[0296] 60, MLA 144, NAMAIWA, NEURO 2A, CHO, PerC.6, YB2 / O, etc., or heteromyeloma, its fusion product, or any cell or fusion cell derived therefrom, or any other suitable cell line as known in the art (see the following websites, such as atcc.org, lifetech.com, last visited on November 26, 2007), the antibody-producing cells such as but not limited to isolated or cloned spleen cells, peripheral blood cells, lymphocytes, tonsil cells or other cells containing immune cells or B cells, or any other cells expressing heavy chain or light chain constant The present invention also can be used to express the cell of the fixed sequence or variable sequence or framework sequence or CDR sequence, they are endogenous or heterologous nucleic acid, recombinant or endogenous, viral, bacterial, algae, prokaryotic, amphibian, insect, reptile, fish, mammal, rodent, horse, ovine, goat, sheep, primate, eukaryotic, genomic DNA, cDNA, rDNA, mitochondrial DNA or RNA, chloroplast DNA or RNA, hnRNA, mRNA, tRNA, single-stranded, double-stranded or triple-stranded, hybrid etc. or any combination thereof. Antibody-producing cells can also be obtained from the peripheral blood of people or other suitable animals that have been immunized with the target antigen and then screened for target activity, or, in specific embodiments, spleen or lymph node. Any other suitable host cell can also be used to express the heterologous or endogenous nucleic acid encoding the antibody of the present invention, its specific fragment or variant. Fusion cells (hybridomas) or recombinant cells can be separated using selective culture conditions or other suitable known methods and cloned by limiting dilution or cell sorting or other known methods.

[0297] Other suitable methods for producing or isolating antibodies with the desired specificity may be used, including but not limited to methods for selecting recombinant antibodies from peptide or protein libraries (e.g., but not limited to, phage, ribosome, oligonucleotide, cDNA, etc. display libraries); for example, libraries are available from various commercial suppliers, such as MorphoSys.

[0298] (Martinsreid / Planegg, Del.), BioInvent (Lund, Sweden), Affitech (Oslo, Norway). Methods known in the art are described in the patent literature, some of which include U.S. Patents 4,704,692; 5,723,323;

[0299] 5,763,192; 5,814,476; 5,817,483; 5,824,514; and 5,976,862. Alternative approaches rely on immunization of transgenic animals (e.g., SCID mice, Nguyen et al. (1977) Microbiol. Immunol. 41:901-907 (1997); Sandhu et al. (1996) Crit, Rev. Biotechnol. 16:95-118; Eren et al. (1998) Mumma 93:154-161) that are capable of producing a repertoire of human antibodies as known in the art and / or as described herein. Such techniques include, but are not limited to, ribosome display (Wanes et al. (1997) Proc. Natl. Acad. Sci. USA 94:4937-4942;

[0300]

[0015] The present invention relates to single-cell antibody production techniques (e.g., the selected lymphocyte antibody method ("SLAM") (US Pat. No. 5,627,052; Wen et al. (1987) J. Immunol 17:887-892; Babcook et al. (1996) Proc. Natl. Acad. Sci. USA 93:7843-7848); gel droplet and flow cytometry (Powell et al. (1990) Biotechnol. 8:333-337; One Cell Systems, (Cambridge, Mass.); Gray et al. (1995) J. Imm. Meth. 182:155-163); and Kenny et al. (1995) Bio. Technol. 13:787-790); B cell screening method (Steenbakkers et al. (1994) Molec. Biol. Reports 19:125-134).

[0301] Antibody derivatives of the present disclosure can also be prepared by delivering a polynucleotide encoding an antibody disclosed herein to a suitable host, for example, to provide a transgenic animal or mammal that produces such antibodies in its emulsion, such as goats, cattle, horses, sheep, etc. These methods are known in the art and are described, for example, in U.S. Patents 5,827,690; 5,849,992; 4,873,316; 5,849,992; 5,994,616; 5,565,362; and 5,304,489.

[0302] The term "antibody derivatives" includes post-translational modifications to the linear polypeptide sequence of an antibody or fragment. For example, U.S. Patent No. 6,602,684B1 describes a method for producing modified diol forms of antibodies, including intact antibody molecules, antibody fragments or fusion proteins, which include a region equivalent to the Fc region of an immunoglobulin, have enhanced Fc-mediated cytotoxicity, and the glycoproteins thus produced.

[0303] The antibodies disclosed herein also include modified derivatives, which are obtained by covalently attaching any type of molecule to the antibody such that the covalent attachment does not prevent the antibody from generating an anti-idiotypic response. Antibody derivatives include, but are not limited to, antibodies that have been modified by glycosylation, acetylation, pegylation, phosphorylation, amidation, derivatization with known protecting / blocking groups, proteolytic cleavage, attachment to cellular ligands or other proteins, and the like. In addition, derivatives may contain one or more non-classical amino acids.

[0304] Antibody derivatives can also be prepared by delivering the polynucleotides disclosed herein to provide transgenic plants and cultured plant cells (such as, but not limited to, tobacco, corn, and duckweed) that produce such antibodies, specific portions, or variants in plant parts or cells cultured therefrom. For example, Cramer et al. (1999) Curr. Top. Microbol. Immunol. 240: 95-118 and references cited therein describe the production of transgenic tobacco leaves expressing large amounts of recombinant proteins using, for example, inducible promoters. Transgenic corn has been used to express mammalian proteins at commercial production levels with biological activities comparable to those produced in other recombinant systems or purified from natural sources. See, for example, Hood et al. (1999) Adv. Exp. Med. Biol. 464: 127-147 and references cited therein. Antibody derivatives, including antibody fragments, such as single-chain antibodies (scFv's), are also produced in large quantities from transgenic plant seeds, including tobacco seeds and potato tubers. See, for example, Conrad et al. (1998) Plant Mol. Biol. 38: 101-109 and references cited therein. Thus, according to known methods, transgenic plants can also be used to produce antibodies.

[0305] Antibody derivatives can also be produced, for example, by adding exogenous sequences to modify immunogenicity or to reduce, enhance, or modify binding, affinity, on-rate, off-rate, avidity, specificity, half-life, or any other suitable characteristic. Typically, some or all of the non-human or human CDR sequences are retained, while the non-human sequences of the variable and constant regions are replaced with human or other amino acids or with variable or constant regions from other isotypes.

[0306] In general, the CDR residues are directly and most substantially involved in influencing antigen binding. Humanization or engineering of antibodies can be performed using any known method, such as, but not limited to, those described in U.S. Patents 5,723,323; 5,976,862; 5,824,514; 5,817,483; 5,814,476; 5,763,192; 5,723,323; 5,766,886; 5,714,352; 6,204,023; 6,180,370; 5,693,762; 5,530,101; 5,585,089; 5,225,539; and 4,816,567.

[0307] Chimeric, humanized or primatized antibodies disclosed herein can be prepared based on the sequence of a reference monoclonal antibody prepared using standard molecular biology techniques. DNA encoding heavy and light chain immunoglobulins can be obtained from a hybridoma of interest and engineered to include non-reference (e.g., human) immunoglobulin sequences using standard molecular biology techniques. For example, to produce chimeric antibodies, mouse variable regions can be connected to human constant regions using methods known in the art (U.S. Patent No. 4,816,567). To produce humanized antibodies, mouse CDR regions can be inserted into human frameworks using methods known in the art (U.S. Patent No. 5,225,539 and U.S. Patent No. 5,530,101; 5,585,089; 5,693,762 and 6,180,370). Similarly, to produce primatized antibodies, mouse CDR regions can be inserted into primate frameworks using methods known in the art (WO 93 / 02108 and WO 99 / 55369).

[0308] The technology for preparing part to fully human antibodies is known in the art and can use any such technology. According to one embodiment, fully human antibody sequences are prepared in the transgenic mice that are engineered to express mankind's heavy chain and light chain antibody genes. Prepared multiple such transgenic mouse strains, they can produce different classes of antibodies. Can merge the B cell from the transgenic mice that produce the required antibody to prepare hybridoma cell line, to continuously produce the required antibody.(See, for example, Russel et al. (2000) Infection and Immunity April 2000: 1820-1826; Gallo et al. (2000) European J. of Immun. 30: 534-540; Green (1999) J. of Immun. Methods 231: 11-23; Yang et al. (1999A) J. of Leukocyte Biology 66: 401-410; Yang (1999B) Cancer Research 59(6): 1236-1243; Jakobovits (1998) Advanced Drug Reviews 31: 33-42; Green and Jakobovits (1998) J. Exp. Med. 188(3): 483-495; Jakobovits (1998) Exp. Opin. Invest. Drugs 7(4): 607-614; Tsuda et al. (1997) Genomics 42: 413-421; Sherman-Gold (1997) Genetic Engineering News 17(14); Mendez et al. (1997) Nature Genetics 15: 146-156; Jakobovits (199б) Weir's Handbook of Experimental Immunology, The Integrated Immune System Vol. IV, 194.1-194.7; Jakobovits (1995) Current Opinion in Biotechnology 6: 561-566; Mendez et al. (1995) Genomics 26: 29y-307; Jakobovits (1994) Current Biology 4(8): 761-763; Arbones et al. (1994) Immunity 1(4): 247-260; Jakobovits (1993) Nature 362(6417): 255-258; Jakobovits et al. (1993) Proc. Natl. Acad. Sci. USA 90(6): 2551-2555; and U.S. Pat. No. 6,075,181.)。

[0309] The antibodies disclosed herein can also be modified to produce chimeric antibodies. Chimeric antibodies are antibodies in which the individual domains of the antibody heavy and light chains are encoded by DNA from multiple species. See, for example, U.S. Patent No. 4,816,567.

[0310] Alternatively, the antibodies disclosed herein can also be modified to produce veneered antibodies. Veneered antibodies are antibodies in which the external amino acid residues of an antibody of one species are judiciously replaced or "veneered" by residues of a second species so that the antibody of the first species will not be immunogenic in the second species, thereby reducing the immunogenicity of the antibody. Since the antigenicity of a protein depends primarily on the properties of its surface, the immunogenicity of an antibody can be reduced by replacing exposed residues that are typically found in another mammalian species. This judicious replacement of external residues should have little or no effect on internal domains or interdomain contacts. Therefore, the ligand binding properties should not be affected by changes that are limited to variable region framework residues. This process is called "veneer" because only the outer surface or skin of the antibody is changed and the supporting residues remain undisturbed.

[0311] The "tiling" procedure takes advantage of the available sequence data for human antibody variable domains (data from Kabat et al.

[0312] (1987) Sequences of Proteins of Immunological Interest, 4th ed., Bethesda, Md., compiled by the National Institutes of Health), updates to this database, and other accessible U.S. and foreign databases (nucleic acid and protein). Non-limiting examples of methods for generating surface antibodies include EP519596; U.S. Patent No. 6,797,492; and described in Padlan et al. (1991) Mol. Immunol. 28(4-5):489-498.

[0313] The term "antibody derivative" also includes "diabodies," which are small antibody fragments with two antigen-binding sites, wherein the fragment comprises a heavy chain variable domain (VH) connected to a light chain variable domain (VL) in the same polypeptide chain. (See, e.g., EP 404,097; WO 93 / 11161; and Hollinger et al. (1993) Proc. Natl. Acad. Sci. USA 90: 6444-6448.) By using a linker that is too short to pair between the two domains on the same chain, these domains are forced to pair with the complementary domains of another chain and create two antigen-binding sites. (See also U.S. Pat. No. 6,632,926 to Chen et al., which discloses antibody variants having one or more amino acids inserted into the hypervariable region of a parent antibody and having a binding affinity for the target antigen that is at least about 2-fold stronger than the binding affinity of the parent antibody for the antigen).

[0314] The term "antibody derivative" also includes engineered antibody molecules, fragments and single domains, such as scFv, dAb, nanobody, minibody, monobody and Affibodies & Hudson (2005) Nature Biotech 23(9): 1126-36; U.S. Patent Application Publication No. 2006 / 0211088; PCT International Application Publication No. WO 2007 / 059782; U.S. Patent No. 5,831,012).

[0315] The term "antibody derivative" further includes "linear antibodies". Procedures for preparing linear antibodies are known in the art and are described in Zapata et al. (1995) Protein Eng. 8(10): 1057-1062. Briefly, these antibodies comprise a pair of tandem Ed segments (VH-C H 1-VH-C H 1), they form a pair of antigen-binding regions. Linear antibodies can be bispecific or monospecific.

[0316] The antibodies disclosed herein can be recovered and purified from recombinant cell culture by known methods, including but not limited to protein A purification, ammonium sulfate or ethanol precipitation, acid extraction, anion or cation exchange chromatography, phosphocellulose chromatography, hydrophobic interaction chromatography, affinity chromatography, hydroxyapatite chromatography, and lectin chromatography. High performance liquid chromatography ("HPLC") can also be used for purification.

[0317] The antibodies disclosed herein include naturally purified products, products of chemical synthesis procedures, and products produced by recombinant techniques from eukaryotic hosts, including, for example, yeast, higher plants, insects, and mammalian cells, or products produced from prokaryotic hosts as described above. Many antibody production systems are described in Birch & Radner (2006) Adv. Drug Delivery Rev. 58: 671-685.

[0318] If the antibody to be tested binds to a protein or polypeptide, then the antibody to be tested is equivalent to the antibody provided by the present invention. It is also possible to determine whether an antibody has the same specificity as the antibody disclosed herein by determining whether the antibody being tested prevents the antibody disclosed herein from binding to the protein or polypeptide with which the antibody typically reacts, without excessive experimentation. If the antibody being tested competes with the antibody disclosed herein, as shown by a reduction in binding of the monoclonal antibody disclosed herein, then the two antibodies may bind to the same or closely related epitopes. Alternatively, the antibody disclosed herein can be pre-incubated with a protein with which it typically reacts, and it is determined whether the ability of the antibody being tested to bind to the antigen is suppressed. If the antibody being tested is suppressed, then it is likely to have the same or closely related epitope specificity as the antibody disclosed herein.

[0319] The term "antibody" is also intended to include antibodies of all immunoglobulin isotypes and subclasses. A specific isotype of a monoclonal antibody can be prepared directly by selection from an initial fusion, or by isolating class-switched variants from a parent hybridoma that secretes a monoclonal antibody of a different isotype using the sib selection technique as described in Steplewski et al. (1985) Proc. Natl. Acad. Sci. USA 82:8653 or Spira et al. (1984) J. Immunol. Methods 74:307. Alternatively, recombinant DNA technology can be used.

[0320] Isolation of other monoclonal antibodies having the specificity of the monoclonal antibodies described herein can also be accomplished by one of ordinary skill in the art by generating anti-idiotypic antibodies. Herlyn et al. (1986) Science 232: 100. Anti-idiotypic antibodies are antibodies that recognize unique determinants present on the monoclonal antibody of interest.

[0321] In some aspects disclosed herein, it will be useful to detectably or therapeutically label antibodies. Suitable labels are described above. Methods for combining antibodies with these reagents are known in the art. For illustrative purposes only, antibodies can be labeled with a detectable moiety, such as a radioactive atom, a chromophore, a fluorophore, or the like. Such labeled antibodies can be used for diagnostic techniques in vivo or in isolated test samples.

[0322] Coupling of an antibody to a low molecular weight hapten can increase the sensitivity of the antibody in the assay. The hapten can then be specifically detected by a second reaction. For example, commonly used haptens are biotin (which reacts with avidin), or dinitrophenol, pyridoxal, and fluorescein, which react with specific anti-hapten antibodies. See Harlow and Lane (1988) above.

[0323] The variable region of the antibody of the present disclosure can be modified by mutating the amino acid residues in VH and / or VL CDR 1, CDR 2 and / or CDR 3 districts to improve one or more binding properties (e.g., affinity) of the antibody. Mutations can be introduced by site-directed mutagenesis or PCR-mediated mutagenesis, and the impact on antibody binding or other functional properties of interest can be assessed in appropriate in vitro or in vivo assays. In certain embodiments, conservative modifications are introduced and generally no more than one, two, three, four or five CDR districts are changed. The mutation can be an amino acid substitution, addition or deletion.

[0324] Framework modifications can be made to antibodies to reduce immunogenicity, for example, by "backmutating" one or more framework residues to the corresponding germline sequence.

[0325] In addition, the antibodies disclosed herein can be engineered to include modifications within the Fc region to alter one or more functional properties of the antibody, such as serum half-life, complement fixation, Fc receptor binding, and / or antigen-dependent cellular cytotoxicity. Such modifications include, but are not limited to, changing the number of cysteine ​​residues in the hinge region to facilitate assembly of light and heavy chains or to increase or decrease the stability of the antibody (U.S. Patent No. 5,677,425), and amino acid mutations in the Fc hinge region to reduce the biological half-life of the antibody (U.S. Patent No. 6,165,745).

[0326] In addition, the antibodies disclosed herein can be chemically modified. The glycosylation of the antibody can be changed, for example, by modifying one or more glycosylation sites within the antibody sequence to increase the affinity of the antibody for the antigen (U.S. Patent Nos. 5,714,350 and 6,350,861). Alternatively, in order to increase antibody-dependent cell-mediated cytotoxicity, low-fucosylated antibodies with reduced fucosylation amounts or antibodies with increased bisecting GlcNac structures can be obtained by expressing the antibody in a host cell with an altered glycosylation machinery (Shields, R. Let al. (2002) J. Biol. Chem. 277: 26733-26740; Umana et al. (1999) Nat. Biotech. 17: 176-180).

[0327] By reacting the antibody or its fragment with polyethylene glycol (PEG) or the reactive ester or aldehyde derivative of PEG under the condition that one or more PEG groups are connected to the antibody or antibody fragment, the antibody disclosed herein can be pegylated to increase biological half-life. Antibody pegylation can be carried out by acylation reaction or alkylation reaction with reactive PEG molecules (or similar reactive water-soluble polymers). As used herein, the term "polyethylene glycol" is intended to encompass any form of PEG that has been used to derive other proteins, such as single (C1-C10) alkoxy- or aryloxy-polyethylene glycol or polyethylene glycol-maleimide. The antibody to be pegylated can be a non-glycosylated antibody. Methods for pegylated proteins are known in the art and can be applied to antibodies disclosed herein (EP 0154316 and EP 0401384).

[0328] In addition, antibodies can be chemically modified by conjugating or fusing their antigen binding regions to serum proteins such as human serum albumin to increase the half-life of the resulting molecule. This approach is described in, for example, EP 0322094 and EP 0486525.

[0329] The antibodies or fragments thereof disclosed herein can be conjugated to diagnostic agents and used for diagnosis, for example, to monitor the development or progression of a disease and to determine the efficacy of a given treatment regimen. Examples of diagnostic agents include enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, radioactive materials, positron-emitting metals using various positron emission tomography methods, and non-radioactive paramagnetic metal ions. The detectable substance can be coupled or conjugated directly to the antibody or fragment thereof, or indirectly coupled or conjugated via a linker using techniques known in the art. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, β-galactosidase, or acetylcholinesterase. Examples of suitable prosthetic group complexes include streptavidin / biotin and avidin / biotin. Examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride, or phycoerythrin. Examples of luminescent materials include luminol. Examples of bioluminescent materials include luciferase, luciferin, and aequorin. Examples of suitable radioactive substances include 125 I. 131I, indium-111, lutetium-171, bismuth-212, bismuth-213, astatine-211, copper-62, copper-64, copper-67, yttrium-90, iodine-125, iodine-131, phosphorus-32, phosphorus-33, scandium-47, silver-111, gallium-67, praseodymium-142, samarium-153, terbium-161, dysprosium-166, holmium-1 The monoclonal antibodies can be conjugated to radioactive metal ions indirectly through the use of bifunctional chelators covalently linked to the antibody. Chelating agents can be chelated via amities (Meares et al. (1984) Anal. Biochem. 142: 68-78); sulfhydryl groups of amino acid residues (Koyama (1994) Chem. Abstr. 120: 217-262); and carbohydrate groups (Rodwell et al. (1986) PNAS USA 83: 2632-2636; Quadri et al.

[0330] (1993) Nucl. Med. Biol. 20:559-570) conjugation.

[0331] In addition, the antibodies or fragments thereof of the present disclosure can be conjugated to therapeutic agents. Suitable therapeutic agents include paclitaxel, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, tenotoposide, vincristine, vinblastine, colchicine, doxorubicin, daunorubicin, dihydroxyanthraquinone, mitoxantrone, mithramycin, actinomycin D, 1-dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, propranolol and puromycin, antimetabolites (such as methotrexate, 6-mercaptopurine, 6-thioguanine, cytarabine), cytosine, ... , fludarabine, 5-fluorouracil, decarbazine, hydroxyurea, asparaginase, gemcitabine, cladribine), alkylating agents (such as chloroethylamine, thiacloprid, chloramphenicol, melphalan, carmustine (BSNU), lomustine (CCNU), cyclophosphamide, busulfan, dibromomannitol, streptozotocin, dacarbazine (DTIC), procarbazine, mitomycin C, cisplatin and other platinum derivatives such as carboplatin), antibiotics (such as dactinomycin (formerly actinomycin), bleomycin, dactinomycin, Erythromycin (formerly daunomycin), doxorubicin, idarubicin, mithramycin, mitomycin, mitoxantrone, plicamycin, anthramycin (AMC), diphtheria toxin and related molecules (e.g., diphtheria A chain and active fragments and hybrid molecules thereof), ricin (e.g., ricin A or deglycosylated ricin A chain toxin), cholera toxin, Shiga-like toxins (SLT-I, SLT-II, SLT-IIV), LT toxin, C3 toxin, Shiga toxin, pertussis toxin, tetanus toxin, soybean Bowman-Birk protease inhibitor, Pseudomonas exotoxin, alorin, saporin, modeccin, gelatin, abrin A chain, modeccin A chain, α-sarcin, Aleurites fordii proteins, dianthus toxin proteins, pokeweed proteins (PAPI, PAPII, and PAP-S), momordica charantia inhibitors, curcin, crotonin, sapaonaria officinalis toxin, officinalis inhibitors, gelonin, mitogellin, restrietocin, phenomycin, enomycin, and mixed toxins.

[0332] Other suitable conjugate molecules include ribonuclease (RNase), DNase I, antisense nucleic acid, inhibitory RNA molecules such as siRNA molecules, immunostimulatory nucleic acids, aptamers, ribozymes, triplex-forming molecules and external guide sequences. Fitamers are small nucleic acids with a length range of 15-50 bases, which can be folded into definite secondary and tertiary structures, such as stem-loop or G-quadruplex, and can be combined with small molecules, such as ATP (U.S. Patent number 5,631,146) and theophylline (U.S. Patent number 5,580,737), and macromolecules, such as reverse transcriptase (U.S. Patent number 5,786,462) and thrombin (U.S. Patent number 5,543,293). Ribozymes are nucleic acid molecules that can catalyze chemical reactions within or between molecules. Ribozymes are usually cut nucleic acid substrates by identification and combination of target substrates and subsequent cutting. Triplex formation functional nucleic acid molecules can interact with double-stranded or single-stranded nucleic acids by forming triplexes, wherein triple-stranded DNA formation depends on the complex of Watson-Crick and Hoogsteen base pairing. The three-stranded molecules can bind to the target region with high affinity and specificity.

[0333] Functional nucleic acid molecules can act as effectors, inhibitors, modulators, and stimulators of a specific activity possessed by a target molecule, or functional nucleic acid molecules can have a de novo activity independent of any other molecules.

[0334] Therapeutic agents can be linked directly or indirectly to antibodies using any of a number of available methods. For example, therapeutic agents can be linked to the hinge region of a reduced antibody component by disulfide bond formation, using a cross-linking agent such as N-succinyl 3-(2-pyridyldithio) propionate (SPDP), or through a carbohydrate portion of the Fc region of the antibody (Yu et al. 1994 Int. J. Cancer 56:244; Upeslacis et al., "Modification of Antibodies by Chemical Methods," in Monoclonal antibodies: principles and applications, Birch et al. (eds.), pages 187-230 (Wiley-Liss, Inc. 1995); Price, "Production and Characterization of Synthetic Peptide-Derived Antibodies," in Monoclonal antibodies: Production, engineering and clinical application, Ritter et al. (eds.), pages 60-84 (Cambridge University Press 1995)).

[0335] The technology of conjugating therapeutic agents to antibodies is well known (Amon et al. "Monoclonal Antibodies For Immunotargeting Of Drugs In Cancer Therapy," in Monoclonal Antibodies And Cancer Therapy; Reisfeld et al. (eds.), pp. 243-56 (Alan R. Liss, Inc. 1985); Hellstrom et al.

[0336] "Antibodies For Drug Delivery," in Controlled Drug Delivery (2nd Ed.); Robinson et al.

[0337] (eds.), pp.623-53 (Marcel Dekker, Inc. 1987); Thorpe "Antibody Carriers OfCytotoxic Agents In Cancer Therapy: A Review," in Monoclonal Antibodies'84: Biological And Clinical Applications, Pinchera et al. (eds.), pp.475-506 (1985); "Analysis, Results, And Future Prospective Of The Therapeutic Use Of Radiolabeled Antibody in Cancer Therapy," in Monoclonal Antibodies For Cancer Detection And Therapy, Baldwin et al. (eds.), pp. 303-16 (Academic Press 1985), and Thorpe et al. "The Preparation And Cytotoxic Properties Of Antibody-ToxinConjugates," (1982) Immunol. Rev. 62:119-58).

[0338] The antibodies disclosed herein or their antigen-binding regions can be linked to another functional molecule, such as another antibody or ligand of a receptor, to produce a bispecific or multispecific molecule that binds to at least two or more different binding sites or target molecules. Antibodies can be linked to one or more other binding molecules (e.g., another antibody, antibody fragment, peptide, or binding mimetic) by, for example, chemical coupling, genetic fusion, or non-covalent binding. In addition to the first and second target epitopes, multispecific molecules can also include a third binding specificity.

[0339] Bispecific and multispecific molecules can be prepared using methods known in the art. For example, each binding unit of a highly specific molecule can be generated separately and then conjugated to each other. When the binding molecule is a protein or peptide, a variety of coupling agents or cross-linking agents can be used for covalent coupling. Examples of cross-linking agents include protein A, carbodiimide, N-succinimidyl-S-acetyl-thioacetate (SATA), 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), o-phthalenedimaleimide (oPDM), N-succinimidyl-3-(2-pyridyldithio) propionate (SPDP), and sulfosuccinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (sulfo-SMCC) (Karpovsky et al. (1984) J. Exp. Med. 160: 1686; Liu et al. (1985) Proc. Natl. Acad. Sci. USA 82: 8648). When the binding molecules are antibodies, they can be conjugated via sulfhydryl bonding of the C-terminal hinge regions of the two heavy chains.

[0340] The antibodies or fragments thereof of the present disclosure can be linked to moieties that are toxic to cells to which the antibody binds to form "depleting" antibodies. These antibodies are particularly useful in applications where depletion of NK cells is desired.

[0341] The antibodies disclosed herein can also be attached to a solid support, which is particularly useful for immunoassays or purification of target antigens. Such solid supports include, but are not limited to, glass, cellulose, polyacrylamide, nylon, polystyrene, polyvinyl chloride, or polypropylene.

[0342] Antibodies can also be combined with many different carriers. Therefore, the present disclosure also provides compositions comprising an antibody and another active or inert substance. Examples of well-known carriers include glass, polystyrene, polypropylene, polyethylene, dextran, nylon, amylase, natural and modified cellulose, polyacrylamide, agarose, and magnetite. For the purposes disclosed herein, the nature of the carrier can be soluble or insoluble. Those skilled in the art will know other suitable carriers for combining monoclonal antibodies, or will be able to determine using routine experimentation.

[0343] In certain aspects, the present disclosure relates to antibodies or antigen-binding fragments that specifically recognize or bind to the head or tail domain, tail fragment, or head fragment of a DNABII protein or fragment thereof. The DNABII protein or fragment thereof can be an IHF or HU polypeptide.

[0344] Functional assays using antibodies

[0345] The antibodies disclosed herein can be used to purify the polypeptides disclosed herein and to identify bioequivalent polypeptides and / or polynucleotides. They can also be used to identify agents that alter the function of the polypeptides disclosed herein. These antibodies include polyclonal antisera, monoclonal antibodies, and various reagents derived from these preparations, which are familiar to those skilled in the art and are described above.

[0346] By adding such neutralizing antibodies to in vivo and in vitro test systems, antibodies that neutralize the activity of proteins encoded by identified genes can also be used in vivo and in vitro to demonstrate their function. They can also be used as agents to modulate the activity of the polypeptides disclosed herein.

[0347] Various antibody preparations can also be used in analytical methods such as ELISA assays or Western blotting to demonstrate expression of the protein encoded by the identified gene in test cells in vitro or in vivo. Fragments of this protein produced by protease degradation during metabolism can also be identified by using appropriate polyclonal antisera and samples from experimental samples.

[0348] The antibodies disclosed herein can be used for vaccination or booster vaccination alone or in combination with peptide- or protein-based vaccines or dendritic cell-based vaccines.

[0349] Diagnosis and treatment methods

[0350] Provided herein is a method for preventing, inhibiting or competing for the binding of DNABII polypeptides or proteins to microbial DNA by contacting DNABII polypeptides or proteins or microbial DNA with an effective amount of one or more reagents as described above (e.g., antibodies disclosed herein or their antigen-binding fragments, polypeptides or CDRs), thereby preventing or inhibiting or competing for the binding of DNABII proteins or polypeptides to microbial DNA. The DNABII polypeptide can be an IHF or HU peptide. In one aspect, the antibody or its antigen-binding fragment selectively binds to the head region of the DNABII polypeptide (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB, and / or the head chimeric peptide IhfA5-mIhfB4 NTHIIn one embodiment, provided herein is an antibody or fragment thereof comprising, or consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 24 or an equivalent thereof, and the LC immunoglobulin variable domain sequence comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 25 or an equivalent thereof. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consists of an amino acid sequence selected from SEQ ID NO: 1, 2, or 3, or an equivalent thereof, and / or a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consists of an amino acid sequence selected from SEQ ID NO: 7, 8, or 9, or an equivalent thereof. In another embodiment, the contacting is performed in vivo or in vitro.

[0351] In another aspect, the antibodies or antigen-binding fragments thereof for use in the methods disclosed herein comprise, consist essentially of, or consist of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consists of a sequence selected from SEQ ID NO: 13, 24 or 26, or an equivalent of each thereof, and / or a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consists of a sequence selected from SEQ ID NO: 14, 25 or 27, or an equivalent of each thereof.

[0352] On the other hand, one or more of DNABII polypeptide disclosed herein and / or microbial DNA and / or its antibody or its Fab and / or polypeptide or CDR are detectably labeled, for example, with a radioisotope or the luminescent molecule that can send a signal when in close contact with each other. Contact can be carried out in vitro or in vivo. These methods can be combined with diagnostic method to detect and / or monitor biofilm formation and / or destruction, for example, using one or more DNABII polypeptides and / or microbial DNA and / or its antibody or its Fab and / or polypeptide or CDR as disclosed herein. On the one hand, described diagnostic method comprises using antibody or Fab as disclosed herein, which specifically binds to the tail region or fragment (including but not limited to: the tail region of IHF or HU, the tail region of IHFA or IHFB, and / or tail chimeric peptide IhfA3-IhfB2) of DNABII polypeptide on the one hand. NTHI ). In another aspect, the antibody or antigen-binding fragment is detectably labeled. In one embodiment, provided herein is an antibody or fragment thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises

[0353] The amino acid sequence of SEQ ID NO: 26 or an equivalent thereof, or consists essentially of, or consists of, the LC immunoglobulin variable domain sequence comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 27 or an equivalent thereof. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, the HC immunoglobulin variable domain sequence comprises, consists essentially of, or consists of an amino acid sequence selected from SEQ ID NO: 4, 5 or 6 or an equivalent thereof, or consists essentially of, or consists of, the LC immunoglobulin variable domain sequence comprises, consists essentially of, or consists of an amino acid sequence selected from SEQ ID NO: 10, 11 or 12 or an equivalent thereof.

[0354] On the other hand, provided herein is a method for destroying microbial biofilm, which destroys microbial biofilm by contacting the biofilm with an effective amount of one or more reagents as described above (such as antibodies or their antigen-binding fragments, polypeptides or CDRs). In one aspect, antibodies or their antigen-binding fragments selectively bind to the head region of DNABII polypeptide (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB, and / or the head chimeric peptide IhfA5-mIhfB4 NTHI). The DNABII polypeptide may be an IHF or HU peptide. In one embodiment, provided herein is an antibody or fragment thereof comprising, or consisting essentially of, or consisting of, a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises the amino acid sequence of SEQ ID NO: 24 or an equivalent thereof, or consists essentially of, or consists of, the LC immunoglobulin variable domain sequence comprises the amino acid sequence of SEQ ID NO: 25 or an equivalent thereof, or consists essentially of, or consists of. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consists of an amino acid sequence selected from SEQ ID NO: 1, 2, or 3, or an equivalent thereof, and / or a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consists of an amino acid sequence selected from SEQ ID NO: 7, 8, or 9, or an equivalent thereof. In another embodiment, the contacting is performed in vivo or in vitro.

[0355] On the one hand, microbial biofilm is produced by the microorganisms that export DNABII polypeptide.DNABII polypeptide can be IHF or HU peptide.On the other hand, one or more of antibody, antibody fragment, DNABII polypeptide and microbial DNA are detectably labeled, for example, with radioisotope or when they are in close contact with each other, they can send out the luminescent molecule label of signal.Contact can be carried out in vitro or in vivo.On the one hand, described reagent is one or more identical or different antibodies and / or Fab.In some embodiments, such antibody or Fab are used alone or in combination with each other, or with reagent other than antibody or other pharmaceutically effective agent alone or in combination with pharmaceutically acceptable carrier.These methods can be combined with diagnostic method, to detect and / or monitor the formation and / or destruction of biofilm.On the one hand, diagnostic method comprises using antibody or Fab as disclosed herein, it specifically binds the tail region or tail fragment (including but not limited to: the tail region of IHF or HU, the tail region of IHFA or IHFB and / or tail chimeric peptide IhfA3-IhfB2) of DNABII polypeptide on the one hand. NTHI ). In another aspect, the antibody or antigen-binding fragment is detectably labeled.

[0356] Also provided herein are methods for preventing biofilm formation on a surface or disrupting a biofilm on a surface, the methods comprising, consisting essentially of, or consisting of treating a susceptible biofilm or a biofilm-containing surface with an effective amount of one or more antibodies, or antigen-binding fragments thereof, polypeptides, or CDRs as described herein, wherein the antibodies, or antigen-binding fragments thereof, bind to the head region of a DNABII peptide (including but not limited to, the head region of IHF or HU, the head region of IHFA or IHFB, and / or the head chimeric peptide IhfA5-mIhfB4); NTHI ). The DNABII polypeptide may be an IHF or HU peptide. In one embodiment, provided herein is an antibody or fragment thereof comprising, or consisting essentially of, or consisting of, a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises the amino acid sequence of SEQ ID NO: 26 or an equivalent thereof, or consists essentially of, or consists of, the LC immunoglobulin variable domain sequence comprises the amino acid sequence of SEQ ID NO: 27 or an equivalent thereof, or consists essentially of, or consists of. In another embodiment, the antibody or fragment thereof comprises, or consists essentially of, or consists of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises, or consists essentially of, or consists of an amino acid sequence selected from SEQ ID NO: 4, 5 or 6 or an equivalent of each thereof, and the LC immunoglobulin variable domain sequence comprises, or consists essentially of, or consists of an amino acid sequence selected from SEQ ID NO: 10, 11 or 12 or an equivalent of each thereof.

[0357] On the one hand, the antibody or Fab comprises a detectable label. These methods can be combined with diagnostic methods to detect and / or monitor the formation and / or destruction of biofilm. On the one hand, diagnostic methods include the use of antibodies or Fabs as disclosed herein, on the one hand, which specifically bind to the tail region or fragment of DNABII polypeptide (including but not limited to: the tail region of IHF or HU, the tail region of IHFA or IHFB, and / or tail chimeric peptide IhfA3-IhfB2 NTHI). In another aspect, the antibody or antigen-binding fragment is detectably labeled. In one embodiment, provided herein is an antibody or fragment thereof comprising, or consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises, or consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 26 or an equivalent thereof, and the LC immunoglobulin variable domain sequence comprises, or consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 27 or an equivalent thereof. In another embodiment, the antibody or fragment thereof comprises, or consists essentially of, or consists of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises, or consists essentially of, or consists of an amino acid sequence selected from SEQ ID NO: 4, 5 or 6 or an equivalent of each thereof, and the LC immunoglobulin variable domain sequence comprises, or consists essentially of, or consists of an amino acid sequence selected from SEQ ID NO: 10, 11 or 12 or an equivalent of each thereof.

[0358] Further provided herein is a method for detecting biofilm in a subject, comprising the following steps, or substantially consisting of, or consisting of: administering to the subject an effective amount of one or more of the antibodies disclosed herein or its fragment, polypeptide or CDR. On the one hand, diagnostic methods include using antibodies or antigen binding fragments as disclosed herein, which specifically bind to the tail region or fragment of the DNABII polypeptide on the one hand (including but not limited to: the tail region of IHF or HU, the tail region of IHFA or IHFB, and / or the tail chimeric peptide IhfA3-IhfB2 NTHI ). The DNABII polypeptide may be an IHF or HU peptide. In another aspect, the antibody or antigen-binding fragment is detectably labeled. In one embodiment, provided herein is an antibody or fragment thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the

[0359] The HC immunoglobulin variable domain sequence comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 26 or an equivalent thereof, and the LC immunoglobulin variable domain sequence comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 27 or an equivalent thereof. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises, consists essentially of, or consists of an amino acid sequence selected from SEQ ID NO: 4, 5, or 6, or an equivalent thereof, and the LC immunoglobulin variable domain sequence comprises, consists essentially of, or consists of an amino acid sequence selected from SEQ ID NO: 10, 11, or 12, or an equivalent thereof.

[0360] Provided herein is a method for preventing or destroying a biofilm in a subject. The method comprises the following criteria, or is substantially composed of, or is composed of: administering to the subject a head region of a binding DNABII peptide disclosed herein (including but not limited to: a head region of IHF or HU, a head region of IHFA or IHFB, and / or a head chimeric peptide IhfA5-mIhfB4 NTHI ) antibodies or fragments thereof. In one aspect, provided herein is a method for preventing or destroying a biofilm in a subject, the method comprising the following steps, or consisting of, or consisting of: administering to the subject an effective amount of one or more antibodies, fragments thereof, polypeptides, or CDRs as disclosed herein, and / or an effective amount of one or more polynucleotides or vectors encoding the antibodies, fragments thereof, polypeptides, or CDRs. The DNABII peptide can be an IHF or HU peptide. In one aspect, the antibody or antigen-binding fragment thereof selectively binds to the head region of the DNABII polypeptide (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB, and / or the head chimeric peptide IhfA5-mIhfB4 NTHIIn one embodiment, provided herein is an antibody or fragment thereof comprising, or consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 24 or an equivalent thereof, and the LC immunoglobulin variable domain sequence comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 25 or an equivalent thereof. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises, consists essentially of, or consists of an amino acid sequence selected from SEQ ID NO: 1, 2, or 3, or an equivalent thereof, and the LC immunoglobulin variable domain sequence comprises, consists essentially of, or consists of an amino acid sequence selected from SEQ ID NO: 7, 8, or 9, or an equivalent thereof. In yet another embodiment, the contacting is performed in vivo or in vitro. The antibody or antigen-binding fragment thereof may be detectably labeled. These methods can be combined with diagnostic methods to detect and / or monitor the formation and / or disruption of biofilms. In one aspect, the diagnostic method comprises using an antibody or antigen-binding fragment as disclosed herein that specifically binds to a tail region or fragment of a DNABII polypeptide (including but not limited to: the tail region of IHF or HU, the tail region of IHFA or IHFB, and / or the tail chimeric peptide IhfA3-IhfB2). NTHI ). In another aspect, the antibody or antigen-binding fragment is detectably labeled.

[0361] Provided herein are methods for treating a condition characterized by biofilm formation in a subject, comprising, consisting essentially of, or consisting of the following steps: administering to the subject a head region of a DNABII polypeptide disclosed herein (including but not limited to a head region of IHF or HU, a head region of IHFA or IHFB, and / or a head chimeric peptide IhfA5-mIhfB4); NTHI) antibody or its fragment. On the one hand, provided herein is a method for preventing or treating a disease characterized by forming a biofilm in a subject, which is by administering an effective amount of one or more of the antibody disclosed herein, its fragment, polypeptide or CDR to the subject, and / or an effective amount of one or more polynucleotides or vectors encoding the antibody, its fragment, polypeptide or CDR. In another aspect, provided herein is a method for suppressing, preventing or treating a microbial infection that produces a biofilm in a subject, the method comprising the following steps, or consisting of the following steps, or consisting of the following steps: administering an effective amount of one or more antibodies, its fragment, polypeptide or CDR as disclosed herein to the subject, and / or an effective amount of one or more polynucleotides or vectors encoding the antibody, its fragment, polypeptide or CDR. The DNABII polypeptide can be an IHF or HU peptide. In one aspect, the antibody or its antigen-binding fragment selectively binds to the head region of the DNABII polypeptide (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB, and / or the head chimeric peptide IhfA5-mIhfB4 NTHI In one embodiment, provided herein is an antibody or fragment thereof comprising, or consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 24 or an equivalent thereof, and the LC immunoglobulin variable domain sequence comprises, consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 25 or an equivalent thereof. In another embodiment, the antibody or its fragment includes a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, or is substantially composed of it, or is composed of it, the HC immunoglobulin variable domain sequence includes an amino acid sequence selected from SEQ ID NO:1, 2 or 3 or an equivalent of each thereof, or is substantially composed of it, or is composed of it, the LC immunoglobulin variable domain sequence includes an amino acid sequence selected from SEQ ID NO:7, 8 or 9 or an equivalent of each thereof, or is substantially composed of it, or is composed of it. In another embodiment, contact is carried out in vivo or in vitro. These methods can be combined with diagnostic methods to detect and / or monitor the formation and / or destruction of biofilm. On the one hand, diagnostic methods include using an antibody or antigen-binding fragment as disclosed herein, which specifically binds to the tail region or tail fragment of DNABII polypeptide on the one hand (including but not limited to: the tail region of IHF or HU, the tail region of IHFA or IHFB, and / or tail chimeric peptide IhfA3-IhfB2 NTHI ). In another aspect, the antibody or antigen-binding fragment is detectably labeled.

[0362] In the above methods, the biofilm is derived from Gram-negative or Gram-positive biofilm-producing bacteria. Non-limiting examples of conditions are selected from the group consisting of chronic non-healing wounds, including venous ulcers and diabetic foot ulcers, ear infections, sinus infections, urinary tract infections, gastrointestinal diseases, lung infections, respiratory tract infections, cystic fibrosis, chronic obstructive pulmonary disease, catheter-related infections, indwelling device-related infections, implant-related infections, osteomyelitis, cellulitis, abscesses, and periodontal disease.

[0363] In certain embodiments of the methods disclosed herein, the administration of one or more of the antibody, its fragment, polypeptide or CDR reduces one or more proinflammatory cytokines in the subject. Non-limiting examples of proinflammatory cytokines include: IL-1β, IL6, IL8, IL12p70, IL17A, interferon (IFN) and tumor necrosis factor (TNF). In addition or alternatively, one or more of the antibody, its fragment, polypeptide or CDR increases one or more anti-inflammatory cytokines in the subject. In one embodiment, anti-inflammatory cytokines include but are not limited to IL10, IL13, IL-1ra, IL-4, IL-11 and transforming growth factor-β (TGF-β).

[0364] Also provided herein are methods for one or more of: inducing a proinflammatory response or treating a condition mediated by a reduced inflammatory response in a subject in need thereof, the method comprising, consisting essentially of, or consisting of: administering to the subject an effective amount of a peptide that binds to the tail region of a DNABII polypeptide (including but not limited to, the tail region of IHF or HU, the tail region of IHFA or IHFB, and / or the tail chimeric peptide IhfA3-IhfB2); NTHI ). The DNABII polypeptide may be an IHF or HU peptide. These methods may be combined with diagnostic methods to detect and / or monitor cytokine release or levels in tissues or subjects. In one aspect, the diagnostic method comprises using an antibody or antigen-binding fragment as disclosed herein that specifically binds to the tail region or tail fragment of a DNABII polypeptide (including but not limited to the tail region of IHF or HU, the tail region of IHFA or IHFB, and / or the tail chimeric peptide IhfA3-IhfB2). NTHI In another aspect, the antibody or antigen-binding fragment is detectably labeled. Non-limiting cytokines include, for example, IL1β, IL6, IL8, IL12p70, IL10, IL13, and IFN.

[0365] Also provided herein are methods for inhibiting a proinflammatory response or treating one or more conditions mediated by an enhanced inflammatory response in a subject in need thereof, the methods comprising, consisting essentially of, or consisting of the following steps: administering to the subject an effective amount of a peptide that binds to the head region of a DNABII polypeptide (including but not limited to the head region of IHF or HU, the head region of IHFA or IHFB, and / or the head chimeric peptide IhfA5-mIhfB4); NTHI ) or an antigen-binding fragment thereof. The DNABII polypeptide may be an IHF or HU peptide. These methods may be combined with diagnostic methods to detect and / or monitor cytokine release or levels in tissues or subjects. In one aspect, the diagnostic method comprises using an antibody or antigen-binding fragment as disclosed herein that specifically binds to the tail region or tail fragment of the DNABII polypeptide (including but not limited to the tail region of IHF or HU, the tail region of IHFA or IHFB, and / or the tail chimeric peptide IhfA3-IhfB2). NTHI In another aspect, the antibody or antigen-binding fragment is detectably labeled. Non-limiting cytokines include, for example, IL1β, IL6, IL8, IL12p70, IL10, IL13, and IFN.

[0366] Additionally or alternatively, provided herein are methods for detecting biofilm on a surface comprising, consisting of, or consisting of the following steps: contacting a surface (in one aspect, a surface susceptible to biofilm or containing biofilm) with an effective amount of one or more antibodies, antigen-binding fragments, polypeptides, or CDRs as described herein, wherein the antibody, fragment, polypeptide, or CDR binds to the tail region or head region of a DNABII peptide (including but not limited to, the head region of IHF or HU, the head region of IHFA or IHFB, the head chimeric peptide IhfA5-mIhfB4, NTHI , the tail region of IHF or HU, the tail region of IHFA or IHFB, and / or the tail chimeric peptide IhfA3-IhfB2 NTHI). In one embodiment, the contacting is performed in vivo or in vitro. In one embodiment, provided herein is an antibody or fragment thereof comprising, or consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises, or consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 26 or an equivalent thereof, and the LC immunoglobulin variable domain sequence comprises, or consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 27 or an equivalent thereof. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consists of an amino acid sequence selected from SEQ ID NO: 4, 5, or 6, or an equivalent thereof, and / or a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consists of an amino acid sequence selected from SEQ ID NO: 10, 11, or 12, or an equivalent thereof. In another aspect, the antibody or antigen-binding fragment is detectably labeled.

[0367] In addition or alternatively, a method for detecting the microbial infection producing biofilm in object is provided herein. The method may further comprise the steps, or be composed of, or be composed of: make one or more of the antibody disclosed herein, its fragment, polypeptide or CDR of effective dose and the thing sample that comprises biofilm separated from object suspect and contact, and detect the combination of described antibody, its fragment, polypeptide or CDR and any biofilm in sample. In one embodiment, described antibody, its fragment, polypeptide or CDR binds to the tail or head region of DNABII peptide (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB, the head chimeric peptide IhfA5-mIhfB4 NTHI , the tail region of IHF or HU, the tail region of IHFA or IHFB, and / or the tail chimeric peptide IhfA3-IhfB2 NTHI). In further embodiments, the contacting is in vivo or in vitro. In one embodiment, provided herein is an antibody or fragment thereof comprising, or consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein the HC immunoglobulin variable domain sequence comprises, or consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 26 or an equivalent thereof, and the LC immunoglobulin variable domain sequence comprises, or consists essentially of, or consists of the amino acid sequence of SEQ ID NO: 27 or an equivalent thereof. In another embodiment, the antibody or fragment thereof comprises, consists essentially of, or consists of a heavy chain (HC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consists of an amino acid sequence selected from SEQ ID NO: 4, 5, or 6, or an equivalent thereof, and / or a light chain (LC) immunoglobulin variable domain sequence comprising, consisting essentially of, or consists of an amino acid sequence selected from SEQ ID NO: 10, 11, or 12, or an equivalent thereof. In another aspect, the antibody or antigen-binding fragment is detectably labeled.

[0368] In addition or alternatively, provided herein is a method for screening an object with biofilm, the method comprising the following steps, or consisting of, consisting of: an effective amount of one or more of an antibody as disclosed herein, its fragment, polypeptide or CDR is contacted with a biological sample comprising biofilm separated from an object, and the combination of the antibody, its fragment, polypeptide or CDR with any biofilm in the sample is detected. In one embodiment, the antibody, its fragment, polypeptide or CDR binds to the tail or head region of a DNABII peptide (including but not limited to: the head region of IHF or HU, the head region of IHFA or IHFB, the head chimeric peptide IhfA5-mIhfB4 NTHI , the tail region of IHF or HU, the tail region of IHFA or IHFB, and / or the tail chimeric peptide IhfA3-IhfB2 NTHI In a further embodiment, the subject in which binding is detected is selected for administration of an effective amount of one or more antibodies, fragments thereof, polypeptides or CDRs as disclosed herein, and / or an effective amount of one or more polynucleotides or vectors encoding the antibodies, fragments thereof, polypeptides or CDRs, wherein the antibodies, fragments thereof, polypeptides or CDRs bind to the head region of the DNABII peptide (including but not limited to the head region of IHF or HU, the head region of IHFA or IHFB, or the head chimeric peptide IhfA5-mIhfB4). NTHIIn yet another embodiment, the contacting is performed in vivo or in vitro. In one embodiment, provided herein is an antibody or fragment thereof comprising, consisting essentially of, or consisting of a heavy chain (HC) immunoglobulin variable domain sequence and / or a light chain (LC) immunoglobulin variable domain sequence, wherein

[0369] The HC immunoglobulin variable domain sequence comprises, con...

Claims

1. An antibody or antigen-binding fragment thereof that specifically binds to the tail region of a DNABII peptide, comprising: (i) a heavy chain complementarity determining region 1 (CDRH1) comprising the sequence GFTFSRY (aa 50 to aa 56 of SEQ ID NO: 4 or 5 or 6 or 26); (ii) a heavy chain complementarity determining region 2 (CDRH2) comprising the sequence SSGGSY (aa 76 to aa 81 of SEQ ID NO: 4 or 5 or 6 or 26); (iii) a heavy chain complementarity determining region 3 (CDRH3) comprising the sequence ER (aa 121 to aa 122 of SEQ ID NO: 4 or 5 or 6 or 26); (iv) a light chain complementarity determining region 1 (CDRL1) comprising the sequence QDISNY (aa47 to aa 52 of SEQ ID NO: 10 or 11 or 12 or 27); (v) a light chain complementary determining region 2 (CDRL2) comprising the sequence YTS (aa 70 to aa 72 of SEQ ID NO: 10 or 11 or 12 or 27); and (vi) a light chain complementarity determining region 3 (CDRL3) comprising the sequence QQ (aa 109 to aa 110 of SEQ ID NO: 10 or 11 or 12 or 27).

2. The antibody or antigen-binding fragment thereof according to claim 1, wherein the antibody or antigen-binding fragment thereof comprises: (i) CDRH1, which consists of the sequence GFTFSRY; (ii) CDRH2, which consists of the sequence SSGGSY; (iii) CDRH3, which consists of the sequence ERHGGDGYWYFDV; (iv) CDRL1, which consists of the sequence QDISNY; (v) CDRL2, which consists of the sequence YTS; and (vi) CDRL3, which consists of the sequence QQGNPLRT.

3. The antibody or antigen-binding fragment thereof according to claim 1 or 2, wherein the antibody or antigen-binding fragment thereof comprises: a heavy chain immunoglobulin variable domain sequence comprising an amino acid sequence at least 90% identical to aa 25 to aa 144 of SEQ ID NO: 4, 5 or 6; and / or a light chain immunoglobulin variable domain sequence comprising an amino acid sequence at least 90% identical to aa 21 to aa 126 of SEQ ID NO: 10, 11 or 12.

4. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 3, wherein the antibody or antigen-binding fragment thereof comprises: a heavy chain immunoglobulin variable domain sequence comprising an amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 4, 5 or 6; and / or a light chain immunoglobulin variable domain sequence comprising an amino acid sequence of aa 21 to aa 126 of SEQ ID NO: 10, 11 or 12.

5. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, wherein the antibody or antigen-binding fragment thereof comprises: a heavy chain immunoglobulin variable domain sequence comprising an amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 4; and a light chain immunoglobulin variable domain sequence comprising an amino acid sequence of aa 21 to aa 126 of SEQ ID NO:

10.

6. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, wherein the antibody or antigen-binding fragment thereof comprises: a heavy chain immunoglobulin variable domain sequence comprising an amino acid sequence of aa 25 to aa 144 of SEQ ID NO:4; and a light chain immunoglobulin variable domain sequence comprising an amino acid sequence of aa 21 to aa 126 of SEQ ID NO:

11.

7. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, wherein the antibody or antigen-binding fragment thereof comprises: a heavy chain immunoglobulin variable domain sequence comprising an amino acid sequence of aa 25 to aa 144 of SEQ ID NO:4; and a light chain immunoglobulin variable domain sequence comprising an amino acid sequence of aa 21 to aa 126 of SEQ ID NO:

12.

8. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, wherein the antibody or antigen-binding fragment thereof comprises: a heavy chain immunoglobulin variable domain sequence comprising an amino acid sequence of aa 25 to aa 144 of SEQ ID NO:5; and a light chain immunoglobulin variable domain sequence comprising an amino acid sequence of aa 21 to aa 126 of SEQ ID NO:

10.

9. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, wherein the antibody or antigen-binding fragment thereof comprises: a heavy chain immunoglobulin variable domain sequence comprising an amino acid sequence of aa 25 to aa 144 of SEQ ID NO:5; and a light chain immunoglobulin variable domain sequence comprising an amino acid sequence of aa 21 to aa 126 of SEQ ID NO:

11.

10. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, wherein the antibody or antigen-binding fragment thereof comprises: a heavy chain immunoglobulin variable domain sequence comprising an amino acid sequence of aa 25 to aa 144 of SEQ ID NO:5; and a light chain immunoglobulin variable domain sequence comprising an amino acid sequence of aa 21 to aa 126 of SEQ ID NO:

12.

11. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, wherein the antibody or antigen-binding fragment thereof comprises: a heavy chain immunoglobulin variable domain sequence comprising an amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 6; and a light chain immunoglobulin variable domain sequence comprising an amino acid sequence of aa 21 to aa 126 of SEQ ID NO:

10.

12. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, wherein the antibody or antigen-binding fragment thereof comprises: a heavy chain immunoglobulin variable domain sequence comprising an amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 6; and a light chain immunoglobulin variable domain sequence comprising an amino acid sequence of aa 21 to aa 126 of SEQ ID NO:

11.

13. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 4, wherein the antibody or antigen-binding fragment thereof comprises: a heavy chain immunoglobulin variable domain sequence comprising an amino acid sequence of aa 25 to aa 144 of SEQ ID NO: 6; and a light chain immunoglobulin variable domain sequence comprising an amino acid sequence of aa 21 to aa 126 of SEQ ID NO:

12.

14. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 13, wherein the antibody further comprises a constant region selected from: an IgA constant region, an IgD constant region, an IgE constant region, an IgG constant region or an IgM constant region.

15. The antibody or antigen-binding fragment thereof according to claim 14, wherein the constant region is an IgG1 constant region.

16. An antigen-binding fragment of the antibody of any one of claims 1-15.

17. The antigen binding fragment of claim 16, wherein the antigen binding fragment is selected from Fab, F(ab')2, Fab', scFv or Fv.

18. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 17, wherein the antibody or antigen-binding fragment thereof is modified by a method selected from PEGylation, polysialylation, HESylation or glycosylation.

19. The antibody or antigen-binding fragment thereof according to any one of claims 1-15 or 18, wherein the antibody is a monoclonal antibody.

20. The antibody or antigen-binding fragment thereof according to any one of claims 1 to 19, further comprising a detectable label.

21. An isolated polynucleotide encoding the antibody or antigen-binding fragment thereof of any one of claims 1-20, and optionally, the isolated polynucleotide is operably linked to a promoter and enhancer elements.

22. A vector comprising the isolated polynucleotide of claim 21.

23. A host cell comprising the polynucleotide of claim 21 or the vector of claim 22.

24. A composition comprising a vector and one or more of the following: an antibody or antigen-binding fragment thereof as described in any one of claims 1-20, an isolated polynucleotide encoding the antibody or antigen-binding fragment thereof, a vector comprising the isolated polynucleotide, or a host cell comprising the isolated polynucleotide.

25. A method for producing the antibody or antigen-binding fragment thereof of any one of claims 1-20, the method comprising culturing a host cell comprising a polynucleotide encoding the antibody or antigen-binding fragment thereof under conditions where the antibody or antigen-binding fragment thereof is expressed, and optionally isolating the antibody or antigen-binding fragment thereof.

26. A method for detecting a biofilm in a subject, comprising administering to the subject the antibody or antigen-binding fragment thereof of any one of claims 1-20, and detecting binding of the antibody or antigen-binding fragment thereof to the biofilm.

27. The method of claim 26, wherein the antibody or antigen-binding fragment thereof is detectably labeled.

28. A non-physiological surface coated with the antibody or antigen-binding fragment thereof according to any one of claims 1 to 20; and Optionally, wherein the surface is in an industrial environment.

29. A kit comprising one or more of the following: an antibody or antigen-binding fragment thereof according to any one of claims 1 to 20, a polynucleotide encoding the antibody or antigen-binding fragment thereof, a vector comprising the polynucleotide, a host cell comprising the polynucleotide, or a composition comprising any one or more of the following: the antibody or antigen-binding fragment thereof, the polynucleotide, the vector or the host cell; and optionally comprising instructions for use.

30. A method of detecting a biofilm-producing microbial infection in a subject, comprising contacting the antibody or antigen-binding fragment thereof of any one of claims 1-20 with a biological sample isolated from the subject.

31. The method of claim 30, wherein the antibody or antigen-binding fragment thereof is detectably labeled.

32. A tail chimeric peptide comprising the amino acid sequence of SEQ ID NO:41 or SEQ ID NO:50.

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