Anti-respiratory syncytial virus antibody cz111-3-183 and uses thereof

Abstract

The application belongs to the field of biological medicine, and particularly relates to an anti-respiratory syncytial virus antibody CZ111-3-183 and application thereof. Specifically, the application provides an antibody or antigen binding fragment thereof specifically binding to a respiratory syncytial virus (RSV) F protein, which has an IC 50 value as low as 0.3230 ng / mL in a neutralization activity test of RSV A2 subtype, and can block 50% of virus infectious unit formation with a trace amount.

Description

Technical Field

[0001] This invention belongs to the field of biomedicine, specifically relating to an anti-respiratory syncytial virus antibody CZ111-3-183 and its uses. Background Technology

[0002] Respiratory syncytial virus (RSV) is a highly contagious and common respiratory RNA virus. It is the leading cause of severe lower respiratory tract infections (bronchitis, pneumonia) in children under 5 years old worldwide, and also poses a serious threat to the elderly and immunocompromised individuals.

[0003] RSV has three glycoproteins on its surface: a small hydrophobic protein (SH), an attachment glycoprotein (G), and a fusion glycoprotein (F). However, only the G and F proteins can induce the production of neutralizing antibodies in the human body. The G protein mainly functions as an adsorption protein, interacting with one or more molecules on the surface of host cells to promote the binding of viral particles to target cells. The main function of the F protein is to mediate the fusion of the viral envelope and the cell membrane. RSV strains are divided into two antigenically different subtypes (RSV-A and RSV-B). The main difference between the two subtypes is the G protein, with 50% amino acid homology. The F protein is relatively conserved, with only 10% difference. Because the F protein has higher sequence conservation than the G protein, it is also the main target protein for developing RSV prevention and treatment methods.

[0004] During the fusion of viral particle membranes with host cell membranes, the F protein undergoes two conformational changes: a metastable pre-fusion conformation (Pre-F, Pre-Fusion) and a stable post-fusion conformation (Post-F, Post-Fusion). In viral translation, the RSV F protein initially appears as an inactive F0 precursor, which is then cleaved by furin protease into two subunits, F1 and F2. These two subunits are covalently linked by disulfide bonds to form a heterodimer, which then binds to HRA and HRB to form a trimer – the Pre-F conformation. Upon stimulation by biological signals, the Pre-F protein undergoes another structural rearrangement, causing the fusion peptide embedded in the Pre-F conformation center to extend and anchor to the host cell membrane surface. It then refolds, allowing HRA and HRB to bind and form a stable six-helix bundle that fuses with the host cell membrane – this is the Post-F conformation. Due to its crucial and highly conserved role in RSV invasion, the RSV F protein is a target for neutralizing antibodies and a major antigen for vaccine development. Neutralizing antibodies targeting Pre-F have greater potential for the prevention and treatment of RSV.

[0005] Currently, there is no active treatment for RSV infection. Clinically, there is an urgent need to develop neutralizing antibodies with higher affinity, stronger neutralizing activity, and broad spectrum coverage of RSV types A and B. Summary of the Invention

[0006] In order to address the problems existing in the prior art, the purpose of this disclosure is to provide an anti-respiratory syncytial virus antibody CZ111-3-183 and its uses.

[0007] To achieve the above objectives, this disclosure adopts the following specific solutions: In one aspect, this disclosure provides an antibody or antigen-binding fragment thereof that specifically binds to the respiratory syncytial virus (RSV) F protein, comprising a heavy chain variable region and a light chain variable region, wherein, The heavy chain variable region comprises: HCDR1 having the amino acid sequence shown in SEQ ID NO: 3 or any variant thereof, HCDR2 having the amino acid sequence shown in SEQ ID NO: 4 or 11 or any variant thereof, and HCDR3 having the amino acid sequence shown in SEQ ID NO: 5 or any variant thereof. The light chain variable region comprises: LCDR1 having the amino acid sequence shown in SEQ ID NO: 16 or 8 or any variant thereof, LCDR2 having the amino acid sequence shown in SEQ ID NO: 17 or 9 or any variant thereof, and LCDR3 having the amino acid sequence shown in SEQ ID NO: 18 or 10 or any variant thereof.

[0008] On the other hand, this disclosure provides a biological material selected from any of the following: (1) A polynucleotide encoding the aforementioned antibody or its antigen-binding fragment; or (2) An expression vector containing the polynucleotide described in (1); or (3) A host cell containing the polynucleotide described in (1) or the expression vector described in (2).

[0009] On the other hand, this disclosure provides a pharmaceutical composition comprising the aforementioned antibody or its antigen-binding fragment, and a pharmaceutically acceptable excipient, diluent, or carrier.

[0010] On the other hand, this disclosure provides a conjugate comprising the aforementioned antibody or its antigen-binding fragment, and a conjugation portion; Preferably, the coupling portion is a purified tag, a detectable label, or a small molecule drug; Preferably, the coupling portion is a fluorescent substance, a chemiluminescent substance, a colored substance, polyethylene glycol, or an enzyme; Preferably, the small molecule drug is an inhibitor of respiratory syncytial virus nucleic acid or F protein.

[0011] On the other hand, this disclosure provides the use of the aforementioned antibodies or antigen-binding fragments thereof, the aforementioned biological materials, the aforementioned pharmaceutical compositions or the aforementioned conjugates in the preparation of medicaments for the treatment or prevention of RSV infection.

[0012] On the other hand, this disclosure provides a method for detecting the presence or content of RSV in a sample, which includes the following steps: The sample is brought into contact with the aforementioned antibody or its antigen-binding fragment, and the formation of an antigen-antibody complex or the amount of such complex is detected.

[0013] On the other hand, this disclosure provides a kit comprising the aforementioned antibody or its antigen-binding fragment, the aforementioned pharmaceutical composition, and / or the aforementioned conjugate; Preferably, the kit further includes a second antibody that specifically recognizes the antibody or its antigen-binding fragment; Optionally, the second antibody further includes a detectable label, including: a radioactive isotope, a fluorescent substance, a chemiluminescent substance, a colored substance, or an enzyme; Preferably, the kit is used to detect the presence or level of RSV in a sample.

[0014] Compared with the prior art, this disclosure has at least the following beneficial effects: In the neutralizing activity assay for RSV A2 subtype, the IC50 of CZ111-3 H1K1 hIgG1 YTE 183 was [missing value]. 50 The value was as low as 0.3230 ng / mL, indicating that only a very small amount of antibody was needed to block 50% of viral infection unit formation. In contrast, the IC50 of the clinical drug Nirsevimab... 50 The value was 26.03 ng / mL. This shows that the neutralizing activity of the antibody of this invention was increased by approximately 80 times. Detailed Implementation

[0015] To more clearly illustrate the technical solutions in the embodiments of this disclosure or the prior art, the terms and implementation methods used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the implementation methods described below are only one implementation method of this disclosure, and other implementation methods can be obtained by those skilled in the art. I. Terminology

[0016] To facilitate understanding of this disclosure, certain technical and scientific terms are specifically defined below. Unless otherwise expressly defined elsewhere in this document, all other technical and scientific terms used herein have the meanings commonly understood by one of ordinary skill in the art to which this disclosure pertains.

[0017] As used herein, the term "about" indicates and covers a specified value and a range greater than and less than that value. In some embodiments, the term "about" may indicate a variation of ±0.1%, ±0.5%, ±1%, ±2%, ±3%, ±4%, ±5%, ±6%, ±7%, ±8%, ±9%, or ±10%. In some embodiments, where applicable, the term "about" indicates a specified value ± one standard deviation of that value.

[0018] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0019] The term “consistently of” or variations thereof, used throughout the specification and claims, means that all said components or groups of components are included, and optionally include other components that are similar to or different in nature from said components, which do not significantly alter or introduce new properties to the specified dosing regimen, method or composition.

[0020] "Optional" or "optionally" means that the event or circumstances described below may, but do not have to, occur, including the circumstances in which the event or circumstances may or may not occur.

[0021] The term "antibody" refers to any form of antibody that exhibits desired biological or binding activity. Therefore, it is used in the broadest sense and specifically includes, but is not limited to, monoclonal antibodies (including full-length monoclonal antibodies), polyclonal antibodies, humanized, fully human antibodies, and chimeric antibodies.

[0022] Typically, the basic antibody structural unit comprises a tetramer. Each tetramer consists of two pairs of identical polypeptide chains, each pair having one "light" chain and one "heavy" chain. The amino-terminal portion of each chain includes a variable region of approximately 100 to 110 or more amino acids primarily responsible for antigen recognition. The carboxyl-terminal portion of the heavy chain defines a constant region primarily responsible for effector function. Human light chains are typically classified as kappa light chains and lambda light chains. Furthermore, human heavy chains are typically classified as mu, delta, gamma, alpha, or epsilon, and antibody isotypes are defined as IgM, IgD, IgG, IgA, and IgE, respectively. In both the light and heavy chains, the variable and constant regions are linked by "J" regions of approximately 12 or more amino acids, and the heavy chain also includes "D" regions of approximately 10 or more amino acids.

[0023] The variable region of each light / heavy chain pair forms the antibody binding site. Therefore, in general, a complete antibody has two binding sites. Except for bifunctional or bispecific antibodies, these two binding sites are usually the same.

[0024] Typically, both heavy and light chains have variable regions containing three highly variable regions, also known as complementarity-determining regions, located within relatively conservative frame regions. CDRs are usually aligned through frame regions, enabling them to bind specific epitopes. Generally, from the N-terminus to the C-terminus, the variable regions of both light and heavy chains include FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4.

[0025] As used herein, the “variable region” of an antibody refers to the variable region of the antibody light chain, either alone or in combination, or the variable region of the antibody heavy chain. As is known in the art, the variable regions of both the heavy and light chains consist of four frame regions (FRs) linked by three complementarity-determining regions (CDRs), also known as hypervariable regions; and facilitate the formation of the antigen-binding site of the antibody. If a variant of the individual variable region is required, particularly in the case of amino acid residue substitutions outside the CDR regions (i.e., within the frame regions), appropriate amino acid substitutions, preferably conserved amino acid substitutions, can be identified by comparing the individual variable region with the variable regions of other antibodies containing CDR1 and CDR2 sequences of the same typical class as the individual variable region.

[0026] As used herein, "antibody fragment" or "antigen-binding fragment" refers to an antigen-binding fragment of an antibody, that is, an antibody fragment that retains the ability to specifically bind to an antigen that binds to the full-length antibody, such as a fragment that retains one or more CDR regions. Examples of antibody-binding fragments include, but are not limited to, Fab, Fab', F(ab')2, and Fv fragments.

[0027] As used herein, "CDR" refers to the complementarity-determining region (CDR) within the variable region of an immunoglobulin. The determination of the CDR and the identification of residues containing antibody binding sites are typically achieved by resolving the structure of the antibody or the antibody-ligand complex. In some embodiments, this can be achieved using any of a variety of techniques known to those skilled in the art, such as X-ray crystallization. In some embodiments, various analytical methods can be employed to identify or estimate the CDR region. Examples of such methods include, but are not limited to, Kabat definition, Chothia definition, AbM definition, contact definition, extension definition, and configuration definition.

[0028] Kabat definition is a standard for numbering residues in antibodies and is commonly used to identify CDR regions. Extended definition is a combination of the Kabat and Chothia definitions. AbM definition uses an integrated suite of computer programs that model antibody structures produced by the Oxford Molecular Group. AbM definition uses a combination of knowledge databases and ab initio algorithms to model the tertiary structure of antibodies derived from primary sequences. Contact definition is based on analysis of available complex crystal structures. While other CDR boundary definitions may not strictly follow any of the above methods, they will still overlap at least partially with the Kabat CDR, but may be shortened or lengthened based on predictions or experimental findings that a particular residue or group of residues does not significantly affect antigen binding. As used herein, CDR can refer to a CDR defined by any method known in the art, including combinations of methods. The methods used herein can utilize CDRs defined according to any of these methods.

[0029] As used herein, the “constant region” of an antibody refers to the constant region of the antibody light chain, either alone or in combination, or the constant region of the antibody heavy chain. The constant region of the IgG heavy chain contains three sequentially ordered immunoglobulin domains (CH1, CH2, and CH3), with the hinge region located between the CH1 and CH2 domains. The constant region of the IgG light chain contains a single immunoglobulin domain (CL).

[0030] As used herein, “Fc domain” refers to the portion of an immunoglobulin (Ig) molecule associated with the crystallizable fragment obtained by digestion of the Ig molecule with papain. As used herein, the term refers to the 2-chain constant regions of an antibody, each chain excluding the first constant region immunoglobulin domain. Within the Fc domain, there are two “Fc chains” (e.g., “first Fc chain” and “second Fc chain”). “Fc chain” generally refers to the C-terminal portion of the antibody heavy chain. Thus, the Fc chain refers to the last two constant region immunoglobulin domains (CH2 and CH3) of the IgA, IgD, and IgG heavy chains, and the last three constant region immunoglobulin domains of the IgE and IgM heavy chains, and optionally the flexible hinges at the N-terminus of these domains.

[0031] Although the boundaries of the Fc chain can vary, the human IgG heavy chain Fc chain is generally defined as containing residues C226 or P230 to its carboxyl terminus, where the numbering is based on the EU index by Edelman et al. and descriptions such as those by Kabat et al. Typically, the Fc chain contains approximately amino acid residues from 236 to 447 of the constant region of the human IgG1 heavy chain. "Fc chain" can refer to the polypeptide alone or in the case of a larger molecule (e.g., in an antibody heavy chain or an Fc fusion protein).

[0032] "Functional Fc domain" refers to an Fc domain that possesses at least one effector function of a native sequence Fc domain. Exemplary "effector functions" include C1q binding; complement-dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; downregulation of cell surface receptors (e.g., B cell receptors); and B cell activation. Such effector functions typically require a combination of an Fc domain and a binding domain (e.g., an antibody variable region), and such antibody effector functions can be assessed using various analyses known in the art.

[0033] A “natural sequence Fc chain” is an Fc chain that contains the same amino acid sequence as the Fc chain found in nature. A “variant Fc chain” contains an amino acid sequence that differs from the amino acid sequence of a natural sequence Fc chain by at least one amino acid modification.

[0034] As used herein, an antibody that "specifically binds" to a particular target protein is an antibody that exhibits preferential binding to that target compared to other proteins, but this specificity does not require absolute binding specificity. An antibody is considered "specific" to its intended target if its binding determines the presence of the target protein in the sample, for example, without producing undesirable results such as false positives. The antibodies or their binding fragments used in this invention will bind to the target protein with an affinity at least two times, preferably at least ten times, more preferably at least 20 times, and most preferably at least 100 times higher than that with non-target proteins.

[0035] As used herein, a "chimeric antibody" refers to an antibody in which a portion of the heavy chain and / or light chain is identical or homologous to the corresponding sequence in an antibody derived from a particular species (e.g., human) or belonging to a particular antibody class or subclass, while the remainder of the chain is identical or homologous to the corresponding sequence in an antibody derived from another species (e.g., mouse) or belonging to another antibody class or subclass, and fragments of such antibodies, provided they exhibit the desired biological activity.

[0036] As used herein, "variants of conserved modifications" or "conservative substitutions" refer to the substitution of an amino acid in a protein with another amino acid having similar characteristics (e.g., charge, side chain size, hydrophobicity / hydrophilicity, main chain conformation, and rigidity), allowing for frequent alterations without changing the protein's biological activity or other desired properties (e.g., antigen affinity and / or specificity). Those skilled in the art will recognize that, in general, a single amino acid substitution in a non-essential region of a polypeptide does not significantly alter its biological activity. Furthermore, substitutions of structurally or functionally similar amino acids are unlikely to disrupt biological activity. Exemplary conserved substitutions are listed in Table 1. Table 1. Exemplary Conserved Amino Acid Replacements

[0037] As used herein, the term “binding affinity” refers to the sum strength of the non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its bound conjugate (e.g., an antigen). Unless otherwise indicated, as used herein, “binding affinity” refers to the intrinsic binding affinity that reflects a 1:1 interaction between members of a binding pair (e.g., antibody and antigen). The affinity of molecule X for its conjugate Y is generally expressed by the dissociation constant (KD). Affinity can be measured using methods commonly known in the art. Low-affinity antibodies generally bind antigens slowly and tend to dissociate readily, while high-affinity antibodies generally bind antigens quickly and tend to remain bound for longer periods. In particular, the term “binding affinity” is intended to refer to the dissociation rate of a particular antigen-antibody interaction. KD, the rate of dissociation, is also called the ratio of the “off-rate” or “kd” to the “on-rate” or “ka”. Therefore, KD is equal to kd / ka and is expressed as a molar concentration (M). Therefore, a smaller KD indicates a stronger binding affinity. Thus, a KD of 1 μM indicates a weaker binding affinity than a KD of 1 nM. The KD value of an antibody can be determined using methods recognized in the art. An exemplary method for determining the KD of an antibody is by using surface plasmon resonance (SPR), typically employing a biosensor system such as the BIACORE system. BIACORE kinetic analysis involves analyzing the binding and dissociation of the antigen with a chip having immobilized molecules (e.g., molecules containing epitope-binding domains) on its surface. Another method for determining the KD of an antibody is by using bio-layer interferometry.

[0038] As used herein, “polynucleotide” or “nucleic acid” (which may be used interchangeably herein) refers to a nucleotide chain of any length, including DNA and RNA. Nucleotides can be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases or their analogues, or any matrix that can be incorporated into the chain by DNA or RNA polymerases. Polynucleotides may contain modified nucleotides, such as methylated nucleotides and their analogues. If present, modifications to the nucleotide structure may be conferred before or after chain assembly. The nucleotide sequence may contain interspersed non-nucleotide components. Polynucleotides may be further modified after polymerization, such as by conjugation with labeled components. Other types of modifications include, for example, “caps”; substitution of one or more naturally occurring nucleotides with analogs; internucleotide modifications, such as those with uncharged bonds (e.g., methyl phosphonate, triphosphate, aminophosphate, carbamate, etc.) and charged bonds (e.g., thiophosphate, dithiophosphate, etc.); those containing side chain portions such as proteins (e.g., nucleases, toxins, antibodies, signal peptides, poly-L-lysine, etc.); those with intercalating agents (e.g., acridine, psoralen, etc.); those containing chelating agents (e.g., metals, radioactive metals, boron, metal oxides, etc.); those containing alkylating agents; those with modified bonds (e.g., α-mutant isomers of nucleic acids, etc.); and unmodified forms of polynucleotides. Furthermore, any hydroxyl group generally present in sugars can be, for example, replaced by phosphonate or phosphate groups, protected by standard protecting groups, or activated to prepare additional bonds with other nucleotides, or conjugated to a solid support. The 5' and 3' terminal OH groups may be phosphorylated or substituted with an amine or organic capping group having 1 to 20 carbon atoms. Other hydroxyl groups may also be derivatized into standard protecting groups. Polynucleotides may also contain similar forms of ribose or deoxyribose known in the art, including, for example, 2'-O-methylribose, 2'-O-allylribose, 2'-fluororibose or 2'-azidoribose, carbocyclic sugar analogs, α- or β-mutantoses, epimeric sugars (such as arabinose, xylose or lythose); piperanose, furanose, sedoheptulose, acyclic analogs and non-basic nucleoside analogs (such as methylriboside).

[0039] As used herein, the terms “cell,” “cell line,” and “cell culture” are used interchangeably, and all such names include their progeny. Therefore, “transformant” and “transformed cell” include the primary test cell and the cultures derived from it, regardless of the number of transfections. It should also be understood that, due to intentional or unintentional mutations, all progeny cannot be exactly identical in terms of DNA content. This includes mutant progeny with the same function or biological activity as those screened in the original transformed cells. Where different names are intended, they are clearly apparent from the context. In the context of expressing a heterologous nucleic acid sequence, “host cell” refers to a prokaryotic or eukaryotic cell (e.g., bacterial cells, yeast cells, mammalian cells, and insect cells) whether in vitro or in vivo. For example, a host cell can be located within a transgenic animal. A host cell can serve as a recipient of a vector and can include any transformable organism capable of replicating the vector and / or expressing the heterologous nucleic acid encoded by the vector.

[0040] As used herein, the term "pharmaceutical composition" refers to a composition administered to a mammalian patient. In a preferred embodiment, the pharmaceutical composition comprises a composition for parenteral injection or infusion. This parenteral injection or infusion may take advantage of a reabsorption process, such as intradermal, subcutaneous, intramuscular, and / or intraperitoneal injection or infusion. Alternatively, the parenteral injection or infusion may bypass the reabsorption process and may be in the form of intracardiac, intraarterial, intravenous, intralumbar, and / or intramembranous injection or infusion. In another preferred embodiment, the pharmaceutical composition comprises a composition for transdermal administration. An example of transdermal administration is epidermal administration, wherein the pharmaceutical composition is administered in the form of a solution, suspension, emulsion, foam, ointment, cream, paste, and / or patch applied to the skin. Alternatively, administration of the pharmaceutical composition may be achieved through one or more mucous membranes. For example, administration may be buccal, lingual, or sublingual, i.e., through the mucous membranes of the mouth and / or tongue, and the application form may be such as tablets, lozenges, sugar-coated tablets (i.e., sugar-coated pills), and / or mouthwash. Optionally, administration may be via the intestines, i.e., through the stomach and / or intestinal mucosa, and in the form of tablets, sugar-coated tablets (i.e., sugar-coated pills), capsules, solutions, suspensions, and / or emulsions. Optionally, administration may be via the rectum, and in the form of suppositories, rectal capsules, and / or ointments or creams. Optionally, administration may be via the nose, and in the form of drops, ointments or creams, and / or sprays. Optionally, administration may be via the lungs, i.e., through the bronchi and / or alveoli, and in the form of aerosols and / or inhalers. Optionally, administration may be via the conjunctiva, and in the form of eye drops, eye ointments, and / or eye washes. Optionally, administration may be via the mucosa of the genitourinary tract, such as through the vagina or urethra, and in the form of suppositories, ointments, and / or pens. It should be understood that the above-mentioned alternative forms of administration are not mutually exclusive, and any combination of them can constitute an effective treatment regimen.

[0041] The pharmaceutical compositions disclosed herein may further include pharmaceutically acceptable carriers. Examples of suitable pharmaceutical carriers are those already known, including phosphate-buffered saline solutions, water, emulsions (such as oil / water emulsions), various wetting agents, sterile solutions, etc. Compositions containing these carriers can be formulated using known conventional methods. These pharmaceutical compositions can be administered to subjects at appropriate doses. Dosing regimens can be determined by the participating physicians and clinical factors. As is known in the medical field, the dose for any given patient depends on many factors, including the patient's size, body surface area, age, the specific compound being administered, sex, time and route of administration, overall health status, and other drugs being administered concurrently. For example, parenteral formulations include sterile water or non-aqueous solutions, suspensions, emulsions, and liposomes. Examples of non-aqueous solvents include propylene glycol, polyethylene glycol, vegetable oils (such as olive oil), and injectable organic lipids (such as ethyl oleate). Carriers include sodium chloride solutions, Ringer's glucose, glucose and sodium chloride, lactated Ringer's, or non-volatile oils. Suitable carriers for intravenous or intra-arterial administration include fluids and nutrient supplements, electrolyte supplements (such as those based on Ringer's glucose), etc. Preservatives and other additives may also be included, such as antimicrobial, antioxidant, chelating agents, inert gases, etc. Additionally, the pharmaceutical compositions of the present invention may contain protein carriers, such as serum albumin or immunoglobulins, preferably human. It is of interest that, in addition to humanized monoclonal antibodies or fragments thereof (as described herein), the pharmaceutical compositions of the present invention may also contain other bioactive agents, depending on the intended use of the pharmaceutical composition. These agents may be drugs acting on the gastrointestinal system, drugs as cell inhibitors, drugs preventing polyuricemia, drugs inhibiting immune responses (such as corticosteroids), drugs modulating inflammatory responses, drugs acting on the circulatory system, and / or existing known agents such as cytokines.

[0042] As used herein, “object,” “individual,” or “patient” refers to an animal in need of treatment that can be affected by the molecules of the present invention.

[0043] As used herein, a "therapeutic effective amount" (or "effective amount") refers to an amount of active ingredient (e.g., the pharmaceutical agent of the present invention) sufficient to produce a beneficial or desired result when applied to a subject or patient. An effective amount may be administered as a single or multiple doses, application, or dosage. Therapeutic effective amounts of the compositions of the present invention can be readily determined by those skilled in the art. In the context of the present invention, a "therapeutic effective amount" is an amount that produces an objectively observed change in one or more parameters related to the treatment of RSV-related diseases, including clinical improvement of symptoms. Of course, the therapeutic effective amount will vary depending on the specific subject and disease to be treated, the subject's weight and age, the severity of disease symptoms, the specific compound selected, the dosing regimen to be followed, the timing of administration, the route of administration, etc., all of which can be readily determined by those skilled in the art.

[0044] As used herein, “treatment” encompasses the comprehensive treatment of a disease or condition. The “treatment” agents of this invention can act in a preventative or protective manner, including comprising a procedure designed for animals identified as at risk (pharmacologically). They can also act in a modified or substantially therapeutic manner, or act to slow the rate or extent of progression of at least one symptom of the disease or condition to be treated. Animals requiring treatment include those already suffering from the condition and those for which prevention is desired. The terms “treatment” or “cure” of a disease or condition include prevention or protection against the disease or condition (i.e., preventing the development of clinical symptoms); suppression of the disease or condition (i.e., halting or inhibiting the development of clinical symptoms); and / or relief of the disease or condition (i.e., causing the clinical symptoms to subside). As to be understood, it is not always possible to distinguish between “prevention” and “suppression” of a disease or condition, as the eventual triggering event may be unknown or potential. Therefore, the term “prevention” should be understood to constitute a class of treatments that encompass both “prevention” and “suppression.” The term “treatment” thus includes “prevention.” II. Detailed Description of Implementation Methods

[0045] In one aspect, this disclosure provides an antibody or antigen-binding fragment thereof that specifically binds to the respiratory syncytial virus (RSV) F protein, comprising a heavy chain variable region and a light chain variable region, wherein, The heavy chain variable region comprises: HCDR1 having the amino acid sequence shown in SEQ ID NO: 3 or any variant thereof, HCDR2 having the amino acid sequence shown in SEQ ID NO: 4 or 11 or any variant thereof, and HCDR3 having the amino acid sequence shown in SEQ ID NO: 5 or any variant thereof. The light chain variable region comprises: LCDR1 having the amino acid sequence shown in SEQ ID NO: 16 or 8 or any variant thereof, LCDR2 having the amino acid sequence shown in SEQ ID NO: 17 or 9 or any variant thereof, and LCDR3 having the amino acid sequence shown in SEQ ID NO: 18 or 10 or any variant thereof.

[0046] In some implementations, the heavy chain variable region includes any of the following: (1) HCDR1 shown in SEQ ID NO: 3, HCDR2 shown in SEQ ID NO: 11, and HCDR3 shown in SEQ ID NO: 5; or, (2) HCDR1 shown in SEQ ID NO: 3, HCDR2 shown in SEQ ID NO: 4, and HCDR3 shown in SEQ ID NO: 5.

[0047] In some implementations, the light chain variable region includes any of the following: (1) LCDR1 as shown in SEQ ID NO: 16, LCDR2 as shown in SEQ ID NO: 17, and LCDR3 as shown in SEQ ID NO: 18; or, (2) LCDR1 as shown in SEQ ID NO: 8, LCDR2 as shown in SEQ ID NO: 9, and LCDR3 as shown in SEQ ID NO: 10.

[0048] In some embodiments, the antibody or its antigen-binding fragment comprises any of the following: (1) The heavy chain variable region includes HCDR1 as shown in SEQ ID NO: 3, HCDR2 as shown in SEQ ID NO: 11, and HCDR3 as shown in SEQ ID NO: 5; the light chain variable region includes LCDR1 as shown in SEQ ID NO: 16, LCDR2 as shown in SEQ ID NO: 17, and LCDR3 as shown in SEQ ID NO: 18; or, (2) The heavy chain variable region includes HCDR1 as shown in SEQ ID NO: 3, HCDR2 as shown in SEQ ID NO: 4, and HCDR3 as shown in SEQ ID NO: 5; the light chain variable region includes LCDR1 as shown in SEQ ID NO: 8, LCDR2 as shown in SEQ ID NO: 9, and LCDR3 as shown in SEQ ID NO: 10.

[0049] In some embodiments, the heavy chain variable region of the antibody or its antigen-binding fragment comprises an amino acid sequence such as SEQ ID NO: 1 or 12, or a variant of an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the aforementioned sequence; and / or The light chain variable region comprises an amino acid sequence such as SEQ ID NO: 6 or 19, or a variant of an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the aforementioned sequence.

[0050] In some embodiments, the antibody or its antigen-binding fragment comprises any of the following: (1) The heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 12, or a variant thereof comprising an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% sequence identity compared to SEQ ID NO: 12; and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 19, or a variant thereof comprising an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% sequence identity compared to SEQ ID NO: 19; or (2) The heavy chain variable region comprises an amino acid sequence as shown in SEQ ID NO: 1, or a variant of an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% sequence identity compared to SEQ ID NO: 1; and the light chain variable region comprises an amino acid sequence as shown in SEQ ID NO: 6, or a variant of an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% sequence identity compared to SEQ ID NO: 6; In some embodiments, the antibody or its antigen-binding fragment comprises any of the following: (1) The heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 12; and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 19; or (2) The heavy chain variable region contains an amino acid sequence as shown in SEQ ID NO: 1; and the light chain variable region contains an amino acid sequence as shown in SEQ ID NO: 6.

[0051] In some embodiments, the antibody or its antigen-binding fragment is selected from any one of murine monoclonal antibodies or their antigen-binding fragments, chimeric antibodies or their antigen-binding fragments, or humanized antibodies or their antigen-binding fragments.

[0052] Preferably, the antibody or its antigen-binding fragment is a humanized antibody or its antigen-binding fragment.

[0053] Preferably, the antibody or its antigen-binding fragment is selected from any one of the following: single-chain Fv (scFv) fragment, Fab fragment, Fab' fragment, F(ab')2, Fv fragment, disulfide bond stable Fv fragment (dsFv), disulfide bond stable scFv (dsscFv), VHH, Fv Fc fusion protein, scFv Fc fusion protein, or scFv Fv fusion protein.

[0054] Preferably, the constant region of the antibody or its antigen-binding fragment is derived from human IgG1; preferably, the constant region has one or more of M252Y, S254T, and T256E; more preferably, it has mutations of M252Y, S254T, and T256E simultaneously.

[0055] In some embodiments, the heavy chain comprises an amino acid sequence such as any one of SEQ ID NO: 14, or a variant comprising an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the aforementioned sequence.

[0056] In some embodiments, the light chain comprises an amino acid sequence such as any one of SEQ ID NO: 21, or a variant of an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the aforementioned sequence.

[0057] Preferably, the antibody comprises a heavy chain and a light chain, the heavy chain comprising the amino acid sequence shown in SEQ ID NO: 14 and the light chain comprising the amino acid sequence shown in SEQ ID NO: 21.

[0058] In some embodiments, the F protein is the F protein in the pre-fusion conformation of type A or type B RSV.

[0059] In some implementations, the RSV includes type A or type B RSV.

[0060] In another respect, this disclosure provides a biological material selected from any of the following: (1) A polynucleotide encoding the aforementioned antibody or its antigen-binding fragment; or (2) An expression vector containing the polynucleotide described in (1); or (3) A host cell containing the polynucleotide described in (1) or the expression vector described in (2).

[0061] In another respect, this disclosure provides a pharmaceutical composition comprising the aforementioned antibody or its antigen-binding fragment, and a pharmaceutically acceptable excipient, diluent, or carrier.

[0062] On the other hand, this disclosure provides a conjugate comprising the aforementioned antibody or its antigen-binding fragment, and a conjugation portion.

[0063] Preferably, the coupling portion is a purified tag, a detectable label, or a small molecule drug.

[0064] Preferably, the coupling portion is a fluorescent substance, a chemiluminescent substance, a colored substance, polyethylene glycol, or an enzyme.

[0065] Preferably, the small molecule drug is an inhibitor of respiratory syncytial virus nucleic acid or F protein.

[0066] In another aspect, this disclosure provides the use of the aforementioned antibody or its antigen-binding fragment, biological material, pharmaceutical composition or conjugate in the preparation of a medicament for the treatment or prevention of RSV infection.

[0067] In some implementations, the drug is used in combination with a second therapeutic agent.

[0068] Preferably, the second therapeutic agent is selected from: antiviral agents, vaccines specific to RSV, siRNAs specific to RSV antigens, or antibodies specific to RSV antigens.

[0069] On the other hand, this disclosure provides a method for detecting the presence or content of RSV in a sample, which includes the following steps: The sample is brought into contact with the aforementioned antibody or its antigen-binding fragment, and the formation of an antigen-antibody complex or the amount of such complex is detected.

[0070] In another aspect, this disclosure provides a kit comprising the aforementioned antibody or its antigen-binding fragment, a pharmaceutical composition and / or conjugate.

[0071] Preferably, the kit further includes a second antibody that specifically recognizes the antibody or its antigen-binding fragment.

[0072] Optionally, the second antibody may further include a detectable marker, including: a radioactive isotope, a fluorescent substance, a chemiluminescent substance, a colored substance, or an enzyme.

[0073] Preferably, the kit is used to detect the presence or level of RSV in a sample.

[0074] In another aspect, this disclosure provides a method for treating or preventing RSV infection, the method comprising administering to a subject an effective amount of the aforementioned antibody or its antigen-binding fragment, biological material, pharmaceutical composition or conjugate.

[0075] On the other hand, this disclosure provides the aforementioned antibodies or their antigen-binding fragments, biological materials, pharmaceutical compositions or conjugates for the treatment or prevention of RSV infection.

[0076] Example The above is a further detailed description of the present invention and should not be considered as a limitation on the specific implementation of the present invention. For those skilled in the art, simple deductions or substitutions without departing from the concept of the present invention are all within the protection scope of the present invention. Example 1: Preparation and Screening of Anti-RSV Neutralizing Antibodies 1. Immunogens and Laboratory Animals

[0077] To obtain highly active neutralizing antibodies that specifically recognize the pre-fusion F protein on the surface of RSV virus, the pre-F glycoprotein of recombinant human RSV A2 strain was specifically selected as the immunogen. This protein was purchased from SinoBiological (catalog number 11049-VNAS). This recombinant protein retains the pre-fusion trimer structure of the natural F protein and is a key antigen for inducing highly active neutralizing antibodies. Five 6-8 week old female BALB / c mice were purchased from Vital River Laboratory Animal Technology Co., Ltd. and housed in an SPF-grade animal facility. 2. Animal Immunization Strategies

[0078] Immunization was administered using a combination of conventional intraperitoneal injection and subcutaneous multi-point injection.

[0079] First immunization (day 0): 50 μg of recombinant RSV Pre-F protein (11049-VNAS) was dissolved in PBS, thoroughly mixed with an equal volume of Freund's complete adjuvant (CFA, Sigma), and emulsified until a stable water-in-oil emulsion was formed. Subcutaneous injections and intraperitoneal injections were administered to each mouse.

[0080] Boosting immunization (days 14, 28, and 42): 25 μg of immunogen was emulsified with an equal volume of Freund's incomplete adjuvant (IFA, Sigma) and then injected intraperitoneally into mice.

[0081] Potency testing and pulse immunization: One week after the third booster immunization, blood was collected via the tail vein, and serum was separated. The binding titer of mouse serum against the RSV Pre-F antigen was detected using an indirect ELISA method. Mice with the highest serum titer were selected for the final pulse immunization. The pulse immunization involved direct intraperitoneal injection of 50 μg of antigen protein to activate splenic B lymphocytes. 3. Cell fusion (hybridoma preparation)

[0082] On day 3 post-immunization, mice were aseptically sacrificed, and spleens were harvested. The spleens were ground in pre-cooled serum-free RPMI-1640 medium and passed through a 70 μm cell sieve to prepare a single-cell suspension. Simultaneously, myeloma cells in logarithmic growth phase (SP2 / 0) were collected and washed twice with serum-free medium. Spleen cells were mixed with SP2 / 0 cells at a ratio of 5:1 to 10:1, and the supernatant was removed by centrifugation. The cells were loosened by gently tapping the bottom of the tube, and 1 mL of PEG1450 (polyethylene glycol, Roche) was slowly added dropwise over 1 minute in a 37°C water bath to induce cell fusion. Serum-free medium was then slowly added to terminate the fusion reaction. The fused cells were collected by centrifugation and resuspended in RPMI-1640 complete medium containing 20% ​​fetal bovine serum and HAT (hypoxanthine, aminopterin, thymine) selection factor. The cell suspension was seeded into 96-well cell culture plates and cultured in a 37°C, 5% CO2 incubator. 4. Antibody screening and identification

[0083] Approximately 10-14 days after fusion, when hybridoma cell colonies are observed to form and cover 1 / 3 to 1 / 2 of the bottom of the well, the supernatant is aspirated for stepwise screening.

[0084] Initial screening: 96-well ELISA plates were coated with immunogen (11049-VNAS) (1 μg / mL, overnight at 4°C). After blocking with 3% BSA, hybridoma culture supernatant was added and incubated for 1 hour. After washing, HRP-labeled goat anti-mouse IgG (secondary antibody) was added, and color development and OD were measured. 450 Positive clones with OD values ​​greater than 3 times those of the negative control were selected for the next round.

[0085] Secondary screening: 96-well ELISA plates were coated with immunogen (11049-VNAS) (1 μg / mL, incubated overnight at 4°C). After blocking with 3% BSA, purified hybridoma culture supernatant (initial concentration 10 μg / mL, 6-fold dilution) was added and incubated for 1 hour. After washing, HRP-labeled goat anti-mouse IgG (secondary antibody) was added, and color development and OD were measured. 450 The values ​​were obtained by using GraphPad Prism to perform four-parameter fitting to obtain the antibody clone binding EC. 50 Select EC 50 Clones superior to nisevivirumab were evaluated. 5. Subcloning and sequencing

[0086] The selected hybridoma cells were subcloned using a three-stage limiting dilution method to ensure the monoclonal nature of the cell lines. Subsequently, total RNA was extracted from the monoclonal hybridoma cells, and the antibody variable region gene was amplified using 5' RACE technology. Sequencing was then performed to obtain the nucleic acid sequences of its heavy chain variable region (VH) and light chain variable region (VL). The clone was named CZ111-3, and its sequence information is shown in Table 2 below. Table 2. Sequence information of the light and heavy chain variable regions of monoclonal antibody CZ111-3

[0087] Example 2: Humanization of anti-RSV neutralizing antibody and Fc functional modification 1. CZ111-3 Humanization

[0088] First, the variable region sequence of the CZ111-3 antibody was compared with the human antibody sequence to identify suitable human germline gene sequences with high homology for antibody determinant cluster (CDR) transplantation. This ensured the antibody binding specificity, and non-human amino acids were replaced. The light chain of the CZ111-3 mouse antibody was mouse IMGT_mVK_14_130, and human IMGT_hVK_1_5, which has the highest homology with its framework region, was selected for CDR transplantation. For FM4, human IGKJ2*01, which has the highest homology, was selected. The heavy chain of the mouse antibody was IGHV1-81, and human germline gene IMGT_hVH_1_18 was selected for CDR transplantation. For FM4, human IGHJ6*01, which has the highest homology, was selected. Simultaneously, computer-aided homology modeling is used to analyze the amino acid sequences of the CDR region and its surrounding framework, avoiding the concentrated distribution of molecular surface charges or hydrophobic regions. By calculating electrostatic forces, van der Waals forces, hydrophilicity / hydrophobicity, and entropy, key amino acid residues in the antibody gene sequence that bind to the target antigen and maintain the spatial structure are identified, and mutation sites are designed based on this. 2. CZ111-3 humanized molecule Fc

[0089] Using the hIgG1 backbone and modifying it with YTE (M252Y / S254T / T256E) molecules, the antibody's ability to bind to the neonatal Fc receptor (FcRn) is enhanced, significantly prolonging the in vivo half-life of the antibody drug, thereby reducing the frequency of administration, improving efficacy and patient compliance.

[0090] The light and heavy chain sequence information of the humanized anti-RSV monoclonal antibody is shown in the table below. Table 3. Sequence information of humanized monoclonal antibodies

[0091] Example 3: In vitro neutralization activity assay

[0092] To evaluate the in vitro neutralizing ability of the humanized anti-RSV monoclonal antibody (CZ111-3 H1K1hIgG1 YTE 183) screened and modified according to this invention against the major circulating subtypes of RSV (subtypes A and B), the clinically approved anti-RSV drug nirsevimab was used as a parallel positive control. The half-maximal inhibitory concentration (IC50) was calculated. 50 This was used to quantify and compare the biological activities of each antibody.

[0093] The day before the experiment, HEp-2 cells in the logarithmic growth phase were digested with trypsin and resuspended in DMEM complete medium containing 10% FBS. Cell counting was performed using a cell counter, and the cell density was adjusted to 2e⁻¹. 5 Cells / mL. Seed the cell suspension into 96-well cell culture plates, 100 μL per well (i.e., 2e). 4 Cells / well. Incubate the cell plate overnight at 37°C in a 5% CO2 incubator until the cells grow into a dense monolayer with 90%-95% confluence. Remove the frozen RSV A2 and RSV B virus solutions and thaw rapidly at 37°C. Determine the virus titer beforehand using the TCID50 method. On the day of the experiment, dilute the virus solution with serum-free DMEM medium to a concentration of approximately 100-150 SFU / 50 μL to ensure that the control wells produce a clear viral infection signal in the absence of antibodies.

[0094] Antibody dilutions were performed in sterile 96-well dilution plates (U-bottom). The initial concentration was set at 1 μg / mL, and serum-free DMEM was used for a 4-fold serial dilution, resulting in 10 concentration gradients. Two replicates were prepared for each concentration. Cell Control (CC) wells containing only cells and Virus Control (VC) wells containing only virus without antibody were also prepared. An equal volume (50 μL) of diluted RSV A2 or RSV B virus solution was added to each well containing antibody at different dilutions. After gentle vortexing, the antibody-virus mixture was incubated at 37°C in a 5% CO2 incubator for 1 hour to allow the antibody to fully bind to and neutralize the F protein on the viral surface.

[0095] Discard the old culture medium from the HEp-2 cell culture plate, wash once with PBS, and gently add 100 μL of covering medium containing 1% methylcellulose to each well. Incubate the cell culture plate statically at 37°C with 5% CO2. Incubate RSV A2 strain for approximately 20-24 hours and RSV B strain for approximately 24-30 hours (the exact time is determined by the formation of small, visible lesions that have not yet fused). Discard the covering medium from the wells and wash twice with PBS. Add 200 μL of pre-chilled 4% paraformaldehyde to each well and fix at room temperature for 15-30 minutes. Discard the fixative and wash three times with PBS containing 0.05% Tween-20 (PBST). Add PBS blocking buffer containing 5% skim milk and incubate at 37°C for 1 hour. Add diluted mouse anti-RSV F protein monoclonal antibody (1:1000 dilution) and incubate at 37°C for 1.5 hours or overnight at 4°C. Wash the plate 3-5 times with PBST. Add HRP-labeled goat anti-mouse IgG secondary antibody and incubate at 37°C for 1 hour. Wash the plate 5 times with PBST to ensure removal of non-specific adsorption. Add 100 μL of TrueBlue™ substrate to each well and incubate at room temperature in the dark for 10-20 minutes until clear blue spots appear. Rinse the wells thoroughly with deionized water to terminate the reaction and air dry the microplate. The dried 96-well plates were imaged at high resolution using a scanner, and the virus inhibition rate at each concentration was calculated using the following formula: Inhibition rate (%) = [1 - (number of spots in sample wells - number of spots in cell control wells) / (number of spots in virus control wells - number of spots in cell control wells)] × 100%.

[0096] Using GraphPad Prism software, with the logarithm of antibody concentration on the x-axis and the inhibition rate on the y-axis, a four-parameter nonlinear regression model was used to fit an S-shaped curve to calculate the IC50. 50 value.

[0097] The experimental results based on the ELISPOT spot counting method are shown in Table 4 below. Table 4. Calculation Results

[0098] The above results indicate that in the RSV A2 subtype test, the IC50 of CZ111-3 H1K1 hIgG1 YTE 183 was [missing information]. 50 The value was as low as 0.3230 ng / mL, indicating that only a very small amount of antibody was needed to block 50% of viral infection unit formation. In contrast, the IC50 of the clinical drug Nirsevimab... 50 The value was 26.03 ng / mL. This shows that the neutralizing activity of the antibody of this invention is increased by approximately 80 times. Furthermore, it also exhibits neutralizing activity against the more difficult-to-neutralize RSV B subtype.

[0099] The above description is merely an embodiment of the present invention and is not intended to limit the present invention in any form or substance. It should be noted that those skilled in the art can make various improvements and additions without departing from the method of the present invention, and these improvements and additions should also be considered within the scope of protection of the present invention. Any modifications, alterations, and equivalent changes made by those skilled in the art based on the above-disclosed technical content without departing from the spirit and scope of the present invention are equivalent embodiments of the present invention. Furthermore, any modifications, alterations, and evolutions made to the above embodiments based on the essential technology of the present invention still fall within the scope of the technical solution of the present invention.

Claims

1. An antibody or antigen-binding fragment thereof that specifically binds to respiratory syncytial virus (RSV) F protein, comprising a heavy chain variable region and a light chain variable region, wherein, The heavy chain variable region comprises: HCDR1 having the amino acid sequence shown in SEQ ID NO: 3 or any variant thereof, HCDR2 having the amino acid sequence shown in SEQ ID NO: 4 or 11 or any variant thereof, and HCDR3 having the amino acid sequence shown in SEQ ID NO: 5 or any variant thereof. The light chain variable region comprises: LCDR1 having the amino acid sequence shown in SEQ ID NO: 16 or 8 or any variant thereof, LCDR2 having the amino acid sequence shown in SEQ ID NO: 17 or 9 or any variant thereof, and LCDR3 having the amino acid sequence shown in SEQ ID NO: 18 or 10 or any variant thereof.

2. The antibody or its antigen-binding fragment according to claim 1, wherein, The heavy chain variable region includes any of the following: (1) HCDR1 shown in SEQ ID NO: 3, HCDR2 shown in SEQ ID NO: 11, and HCDR3 shown in SEQ ID NO: 5; or, (2) HCDR1 shown in SEQ ID NO: 3, HCDR2 shown in SEQ ID NO: 4, and HCDR3 shown in SEQ ID NO: 5; Preferably, the light chain variable region comprises any of the following: (1) LCDR1 as shown in SEQ ID NO: 16, LCDR2 as shown in SEQ ID NO: 17, and LCDR3 as shown in SEQ ID NO: 18; or, (2) LCDR1 as shown in SEQ ID NO: 8, LCDR2 as shown in SEQ ID NO: 9, and LCDR3 as shown in SEQ ID NO:

10.

3. The antibody or its antigen-binding fragment according to claim 1 or 2, wherein, (1) The heavy chain variable region includes HCDR1 as shown in SEQ ID NO: 3, HCDR2 as shown in SEQ ID NO: 11, and HCDR3 as shown in SEQ ID NO: 5; the light chain variable region includes LCDR1 as shown in SEQ ID NO: 16, LCDR2 as shown in SEQ ID NO: 17, and LCDR3 as shown in SEQ ID NO: 18; or, (2) The heavy chain variable region includes HCDR1 as shown in SEQ ID NO: 3, HCDR2 as shown in SEQ ID NO: 4, and HCDR3 as shown in SEQ ID NO: 5; the light chain variable region includes LCDR1 as shown in SEQ ID NO: 8, LCDR2 as shown in SEQ ID NO: 9, and LCDR3 as shown in SEQ ID NO:

10.

4. The antibody or antigen-binding fragment thereof according to any one of claims 1-3, wherein, The heavy chain variable region comprises an amino acid sequence such as SEQ ID NO: 1 or 12, or a variant comprising an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the aforementioned sequence; and / or The light chain variable region comprises an amino acid sequence such as SEQ ID NO: 6 or 19, or a variant of an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the aforementioned sequence. Preferably, the antibody or its antigen-binding fragment comprises any one of the following: (1) The heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 12, or a variant thereof comprising an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% sequence identity compared to SEQ ID NO: 12; and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 19, or a variant thereof comprising an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% sequence identity compared to SEQ ID NO: 19; or (2) The heavy chain variable region comprises an amino acid sequence as shown in SEQ ID NO: 1, or a variant of an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% sequence identity compared to SEQ ID NO: 1; and the light chain variable region comprises an amino acid sequence as shown in SEQ ID NO: 6, or a variant of an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% sequence identity compared to SEQ ID NO: 6; Preferably, the antibody or its antigen-binding fragment comprises any one of the following: (1) The heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO: 12; and the light chain variable region comprises the amino acid sequence shown in SEQ ID NO: 19; or (2) The heavy chain variable region contains an amino acid sequence as shown in SEQ ID NO: 1; and the light chain variable region contains an amino acid sequence as shown in SEQ ID NO:

6.

5. The antibody or antigen-binding fragment thereof according to any one of claims 1-4, wherein, The antibody or its antigen-binding fragment includes any one of a murine monoclonal antibody or its antigen-binding fragment, a chimeric antibody or its antigen-binding fragment, or a humanized antibody or its antigen-binding fragment. Preferably, the antibody or its antigen-binding fragment is a humanized antibody or its antigen-binding fragment; Preferably, the antibody or its antigen-binding fragment is selected from any one of the following: single-chain Fv (scFv) fragment, Fab fragment, Fab' fragment, F(ab')2, Fv fragment, disulfide bond stable Fv fragment (dsFv), disulfide bond stable scFv (dsscFv), VHH, Fv Fc fusion protein, scFv Fc fusion protein, or scFv Fv fusion protein; Preferably, the constant region of the antibody or its antigen-binding fragment is derived from human IgG1; preferably, the constant region has one or more of M252Y, S254T, and T256E; more preferably, the constant region has mutations of M252Y, S254T, and T256E simultaneously.

6. The antibody or antigen-binding fragment thereof according to any one of claims 1-5, wherein, The heavy chain comprises an amino acid sequence such as any one of SEQ ID NO: 14, or a variant comprising an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the aforementioned sequence. Preferably, the light chain comprises an amino acid sequence such as any one of SEQ ID NO: 21, or a variant of an amino acid sequence having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity with the aforementioned sequence; Preferably, the antibody comprises a heavy chain and a light chain, the heavy chain comprising the amino acid sequence shown in SEQ ID NO: 14; and the light chain comprising the amino acid sequence shown in SEQ ID NO:

21.

7. The antibody or antigen-binding fragment thereof according to any one of claims 1-6, wherein, The F protein is the pre-fusion conformation F protein; Preferably, the RSV includes type A or type B RSV.

8. A biological material selected from any one of the following: (1) A polynucleotide encoding an antibody or an antigen-binding fragment thereof as described in any one of claims 1-7; or (2) An expression vector containing the polynucleotide described in (1); or (3) A host cell containing the polynucleotide described in (1) or the expression vector described in (2).

9. A pharmaceutical composition comprising an antibody or an antigen-binding fragment thereof as described in any one of claims 1-7, and a pharmaceutically acceptable excipient, diluent, or carrier.

10. A conjugate comprising the antibody or antigen-binding fragment thereof as described in any one of claims 1-7, and a conjugation portion; Preferably, the coupling portion is a purified tag, a detectable label, or a small molecule drug; Preferably, the coupling portion is a fluorescent substance, a chemiluminescent substance, a colored substance, polyethylene glycol, or an enzyme; Preferably, the small molecule drug is an inhibitor of respiratory syncytial virus nucleic acid or F protein.

11. Use of the antibody or antigen-binding fragment thereof according to any one of claims 1-7, the biomaterial according to claim 8, the pharmaceutical composition according to claim 9, or the conjugate according to claim 10 in the preparation of a medicament for treating or preventing RSV infection.

12. The use according to claim 11, wherein, The drug is used in combination with a second therapeutic agent; Preferably, the second therapeutic agent is selected from: antiviral agents, vaccines specific to RSV, siRNAs specific to RSV antigens, or antibodies specific to RSV antigens.

13. A method for detecting the presence or content of RSV in a sample, comprising the following steps: The sample is brought into contact with the antibody or its antigen-binding fragment as described in any one of claims 1-7, and the formation of an antigen-antibody complex or the amount of the formed antigen-antibody complex is detected.

14. A kit comprising the antibody or antigen-binding fragment thereof according to any one of claims 1-7, the pharmaceutical composition according to claim 9, and / or the conjugate according to claim 10; Preferably, the kit further includes a second antibody that specifically recognizes the antibody or its antigen-binding fragment; Optionally, the second antibody further includes a detectable marker, including: Radioactive isotopes, fluorescent substances, chemiluminescent substances, colored substances, or enzymes; Preferably, the kit is used to detect the presence or level of RSV in a sample.

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