Anti-varicella-zoster virus antibody and application thereof

Abstract

The invention discloses an antibody for resisting varicella-zoster virus and application of the antibody. A heavy chain variable region of the antibody comprises HCDR1, HCDR2 and HCDR3 which are respectively shown as SEQ ID NO: 42 to 44, SEQ ID NO: 7 to 9, SEQ ID NO: 13 to 15, SEQ ID NO: 19 to 21, SEQ ID NO: 30 to 32 or SEQ ID NO: 36 to 38; and / or the light chain variable region of the antibody comprises LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO: 45, 5 and 46, SEQ ID NO: 10 to 12, SEQ ID NO: 16 to 18, SEQ ID NO: 22 to 24, SEQ ID NO: 33 to 35 or SEQ ID NO: 39 to 41 respectively. The neutralizing effect IC50 value of the antibody on the VZV virus can reach 0.18 mu g / mL.

Description

Technical Field

[0001] This invention relates to the field of immunotherapy, specifically to antibodies against varicella-zoster virus and their applications. Background Technology

[0002] Varicella-zoster virus (VZV) belongs to the Herpesviridae family, Alphaherpesvirinae subfamily. It is an enveloped double-stranded DNA virus that causes both varicella (chickenpox) and herpes zoster (HZ) after infection, with a global infection rate >90%. VZV virus includes six glycoproteins: gE, gB, gH, gI, gC, and gL. Glycoproteins gE, gB, and gH are extremely abundant in infected cells and are also present in the virion cell membrane. Varicella-zoster virus gE is an essential glycoprotein of VZV. gE antibodies neutralize the virus in vitro, and immunization with a vector expressing gE can protect animals from viral attack. Furthermore, varicella-zoster virus gE is involved in viral entry and intercellular transmission.

[0003] VZV is a highly contagious pathogen that causes chickenpox upon initial infection, and the population is generally susceptible (infection rate approximately 61%-100%). The virus can remain latent in the dorsal root ganglia, persisting throughout life. In areas with low VZV prevalence, coupled with the rising age distribution of chickenpox cases leading to a large number of women of childbearing age being VZV IgG seronegative, the chances of contracting chickenpox during this period increase, posing a significant risk to both the mother and the developing infant. Furthermore, the most common complication of chickenpox during pregnancy is maternal pneumonia, which can be life-threatening if not treated properly. Related symptoms such as cough, chest pain, fever, fatigue, and shortness of breath can worsen in late pregnancy. Approximately 10%-20% of pregnant women with acute chickenpox will develop pneumonia. Complications in the fetus and newborn include congenital varicella syndrome, a relatively rare disease that can cause low birth weight (intrauterine growth retardation), scarring of the skin on the arms and legs, and abnormal brain function in affected newborns. The severity of the disease varies greatly depending on when the maternal infection occurs during fetal development. It is estimated that about 1%-2% of maternal varicella infections contracted within the first 20 weeks of pregnancy will result in congenital varicella syndrome.

[0004] Reactivation of latent VZV virus manifests as herpes zoster, frequently occurring in the elderly and immunocompromised adults, particularly after age 50, which is related to age-related decline in cellular immunity. Overlapping lesions in adjacent dermatomes occur in 20% of patients. The most commonly affected dermatomes are the thoracic spine, followed by the skull (especially the trigeminal nerve), lumbar spine, and cervical spine. Postherpetic neuralgia (PHN) is severe and can last for years, with both incidence and severity increasing with age. A systematic review found that the incidence of herpes zoster in Europe and America is 3-5 per 1000 people per year, and the incidence in people aged 60 and above is 6-12 per 1000 people per year. With the increasing aging of the population, the public health problem of herpes zoster will become increasingly prominent.

[0005] Vaccination is the most economical and effective measure to prevent varicella-zoster virus (VZV). However, patients with weakened immune systems may not receive a sufficient protective response from vaccination. Studies have shown that premature infants are at risk of contracting varicella starting at 6 months of age, while children under 1 year old are not yet eligible for the VZV vaccine. Currently, passive immunization against varicella in high-risk groups primarily utilizes imported VZV-specific immunoglobulins (such as VariZIG), which can reduce the risk of VZV infection and prevent and mitigate severe VZV infection. Because immunoglobulins are blood products, they are inherently scarce and subject to batch-to-batch variability, and pose a risk of transmitting bloodborne pathogens.

[0006] In recent years, significant progress has been made in antibody therapy for VZV. Antibody therapy is relatively safe, has fewer side effects, and can be combined with other treatments, such as antiviral drugs and immunomodulators, to enhance therapeutic efficacy. This comprehensive treatment strategy can better control viral replication and spread, reduce the occurrence of complications, and provide patients with a new and comprehensive treatment option. Clinical trials have shown that antibody therapy has potential for treating shingles and preventing chickenpox recurrence. Summary of the Invention

[0007] To address the technical problem of the lack of an effective, relatively safe antibody against varicella-zoster virus (VZV) with few side effects in existing technologies, this invention provides an antibody against VZV and its application. This invention provides a safer, more effective, and mass-producible drug for the prevention and treatment of VZV.

[0008] A first aspect of the present invention provides an antibody against varicella-zoster virus or an antigen-binding fragment thereof, characterized in that the antibody or antigen-binding fragment comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises amino acid sequences HCDR1, HCDR2, and HCDR3 as shown in SEQ ID NO:42, 43, and 44, respectively; and the light chain variable region comprises amino acid sequences LCDR1, LCDR2, and LCDR3 as shown in SEQ ID NO:45, 5, and 46, respectively; or,

[0009] The heavy chain variable region comprises amino acid sequences HCDR1, HCDR2, and HCDR3 as shown in SEQ ID NO:7, 8, and 9, respectively; and the light chain variable region comprises amino acid sequences LCDR1, LCDR2, and LCDR3 as shown in SEQ ID NO:10, 11, and 12, respectively; or,

[0010] The heavy chain variable region comprises the amino acid sequences HCDR1, HCDR2, and HCDR3 as shown in SEQ ID NO:13, 14, and 15, respectively; and the light chain variable region comprises the amino acid sequences LCDR1, LCDR2, and LCDR3 as shown in SEQ ID NO:16, 17, and 18, respectively; or,

[0011] The heavy chain variable region comprises the amino acid sequences HCDR1, HCDR2, and HCDR3 as shown in SEQ ID NO:19, 20, and 21, respectively; and the light chain variable region comprises the amino acid sequences LCDR1, LCDR2, and LCDR3 as shown in SEQ ID NO:22, 23, and 24, respectively; or,

[0012] The heavy chain variable region comprises the amino acid sequences HCDR1, HCDR2, and HCDR3 as shown in SEQ ID NO:30, 31, and 32, respectively; and the light chain variable region comprises the amino acid sequences LCDR1, LCDR2, and LCDR3 as shown in SEQ ID NO:33, 34, and 35, respectively; or,

[0013] The heavy chain variable region comprises the amino acid sequences HCDR1, HCDR2, and HCDR3 as shown in SEQ ID NO:36, 37, and 38, respectively; and the light chain variable region comprises the amino acid sequences LCDR1, LCDR2, and LCDR3 as shown in SEQ ID NO:39, 40, and 41, respectively.

[0014] In some embodiments of the present invention, the heavy chain variable region comprises the amino acid sequences HCDR1, HCDR2, and HCDR3 as shown in SEQ ID NO:1, 2, and 3, respectively; and the light chain variable region comprises the amino acid sequences LCDR1, LCDR2, and LCDR3 as shown in SEQ ID NO:4, 5, and 6, respectively; or,

[0015] The heavy chain variable region comprises the amino acid sequences HCDR1, HCDR2, and HCDR3 as shown in SEQ ID NO:25, 26, and 27, respectively; and the light chain variable region comprises the amino acid sequences LCDR1, LCDR2, and LCDR3 as shown in SEQ ID NO:28, 5, and 29, respectively.

[0016] In some embodiments of the present invention, the framework region of the heavy chain variable region and / or the light chain variable region is a human-derived framework region.

[0017] In some preferred embodiments of the present invention, the heavy chain variable region comprises an amino acid sequence as shown in SEQ ID NO:47 or has at least 80%, 90%, 95%, or 99% identity with an amino acid sequence as shown in SEQ ID NO:47; and / or, the light chain variable region comprises an amino acid sequence as shown in SEQ ID NO:48 or has at least 80%, 90%, 95%, or 99% identity with an amino acid sequence as shown in SEQ ID NO:48; or,

[0018] The heavy chain variable region comprises an amino acid sequence as shown in SEQ ID NO:49 or has at least 80%, 90%, 95%, or 99% identity with an amino acid sequence as shown in SEQ ID NO:49; and / or, the light chain variable region comprises an amino acid sequence as shown in SEQ ID NO:50 or has at least 80%, 90%, 95%, or 99% identity with an amino acid sequence as shown in SEQ ID NO:50; or,

[0019] The heavy chain variable region comprises an amino acid sequence as shown in SEQ ID NO:51 or has at least 80%, 90%, 95%, or 99% identity with an amino acid sequence as shown in SEQ ID NO:51; and / or, the light chain variable region comprises an amino acid sequence as shown in SEQ ID NO:52 or has at least 80%, 90%, 95%, or 99% identity with an amino acid sequence as shown in SEQ ID NO:52; or,

[0020] The heavy chain variable region comprises an amino acid sequence as shown in SEQ ID NO:53 or has at least 80%, 90%, 95%, or 99% identity with an amino acid sequence as shown in SEQ ID NO:53; and / or, the light chain variable region comprises an amino acid sequence as shown in SEQ ID NO:54 or has at least 80%, 90%, 95%, or 99% identity with an amino acid sequence as shown in SEQ ID NO:54; or,

[0021] The heavy chain variable region comprises an amino acid sequence as shown in SEQ ID NO:55 or has at least 80%, 90%, 95%, or 99% identity with an amino acid sequence as shown in SEQ ID NO:55; and / or, the light chain variable region comprises an amino acid sequence as shown in SEQ ID NO:56 or has at least 80%, 90%, 95%, or 99% identity with an amino acid sequence as shown in SEQ ID NO:56; or,

[0022] The heavy chain variable region comprises an amino acid sequence as shown in SEQ ID NO:57 or has at least 80%, 90%, 95%, or 99% identity with an amino acid sequence as shown in SEQ ID NO:57; and / or, the light chain variable region comprises an amino acid sequence as shown in SEQ ID NO:58 or has at least 80%, 90%, 95%, or 99% identity with an amino acid sequence as shown in SEQ ID NO:58; or,

[0023] The heavy chain variable region comprises an amino acid sequence as shown in SEQ ID NO:59 or has at least 80%, 90%, 95%, or 99% identity with an amino acid sequence as shown in SEQ ID NO:59; and / or, the light chain variable region comprises an amino acid sequence as shown in SEQ ID NO:60 or has at least 80%, 90%, 95%, or 99% identity with an amino acid sequence as shown in SEQ ID NO:60;

[0024] The above technical solutions only change the frame region of the antibody variable region, while the CDR region remains unchanged, and the changes to the frame region of the antibody variable region maintain or improve the original activity of the antibody.

[0025] In some embodiments of the present invention, the antibody against varicella-zoster virus or its antigen-binding fragment is any of the following antibody forms:

[0026] (a) A full-length antibody;

[0027] (b) A type of scFv;

[0028] (c) A fusion protein containing scFv;

[0029] (d) A Fab fragment;

[0030] (e) a Fab′ fragment; and,

[0031] (f) A type of F(ab)2;

[0032] Alternatively, the antibody against varicella-zoster virus or its antigen-binding fragment may be a monoclonal antibody or a polyclonal antibody.

[0033] Alternatively, the antibody against varicella-zoster virus or its antigen-binding fragment may be a humanized antibody and / or a bispecific antibody.

[0034] In some preferred embodiments of the present invention, the antibody or its antigen-binding fragment is a full-length antibody whose heavy chain constant region and / or light chain constant region are derived from human antibodies.

[0035] In some preferred embodiments of the present invention, the heavy chain constant region is derived from the human IgG1 constant region; and / or, the light chain constant region is derived from the human light chain κ chain constant region or λ chain constant region.

[0036] A second aspect of the present invention provides a chimeric antigen receptor comprising an antibody against varicella-zoster virus as described in the first aspect of the present invention, or an antigen-binding fragment thereof.

[0037] A third aspect of the present invention provides an isolated nucleic acid encoding an antibody against varicella-zoster virus as described in the first aspect of the present invention, or an antigen-binding fragment thereof, or a chimeric antigen receptor as described in the second aspect of the present invention.

[0038] A fourth aspect of the present invention provides a recombinant expression vector comprising the nucleic acid as described in the third aspect of the present invention.

[0039] In some preferred embodiments of the present invention, the recombinant expression vector is a plasmid, granule, bacteriophage, or viral vector.

[0040] In some preferred embodiments of the present invention, the viral vector is a baculovirus vector, a retrovirus vector, a lentivirus vector, an adenovirus vector, or an adeno-associated virus vector; the plasmid backbone is pcDNA3.4.

[0041] A fifth aspect of the present invention provides a transformant comprising, in a host cell, a recombinant expression vector as described in the fourth aspect of the present invention.

[0042] In some preferred embodiments of the present invention, the host cell is a prokaryotic cell or a eukaryotic cell.

[0043] In some preferred embodiments of the present invention, the host cell is selected from yeast cells, insect cells, mammalian cells, or other cells suitable for antibodies.

[0044] In some preferred embodiments of the present invention, the lactating cells are HEK293 cells.

[0045] A sixth aspect of the present invention provides a method for preparing an antibody against varicella-zoster virus or an antigen-binding fragment thereof, comprising culturing a transformant as described in the fifth aspect of the present invention, and obtaining the antibody against varicella-zoster virus or an antigen-binding fragment thereof from the culture.

[0046] A seventh aspect of the present invention provides an antibody-drug conjugate comprising a cytotoxic agent and an antibody against varicella-zoster virus or an antigen-binding fragment thereof as described in the first aspect of the present invention.

[0047] An eighth aspect of the present invention provides a pharmaceutical composition comprising an antibody against varicella-zoster virus as described in the first aspect of the present invention, an antigen-binding fragment thereof, a chimeric antigen receptor as described in the second aspect of the present invention, or an antibody-drug conjugate as described in the seventh aspect of the present invention, and a pharmaceutically acceptable carrier.

[0048] The ninth aspect of the present invention provides the use of an antibody against varicella-zoster virus as described in the first aspect of the present invention, or an antigen-binding fragment thereof, as described in the second aspect of the present invention, a chimeric antigen receptor as described in the third aspect of the present invention, a recombinant expression vector as described in the fourth aspect of the present invention, a transformant as described in the fifth aspect of the present invention, an antibody-drug conjugate as described in the seventh aspect of the present invention, or a pharmaceutical composition as described in the eighth aspect of the present invention in the preparation of a medicament for the prevention or treatment of varicella-zoster virus.

[0049] A tenth aspect of the present invention provides a kit comprising an antibody against varicella-zoster virus as described in the first aspect of the present invention, an antigen-binding fragment thereof, a chimeric antigen receptor as described in the second aspect of the present invention, an antibody-drug conjugate as described in the seventh aspect of the present invention, or a pharmaceutical composition as described in the eighth aspect of the present invention.

[0050] The eleventh aspect of the present invention provides a kit comprising a kit A and a kit B, wherein the kit A contains an antibody against varicella-zoster virus as described in the first aspect of the present invention or an antigen-binding fragment thereof and / or a pharmaceutical composition as described in the eighth aspect of the present invention;

[0051] Box B contains other drug compositions for the prevention or treatment of varicella-zoster, and / or other drugs for the prevention or treatment of varicella-zoster.

[0052] A twelfth aspect of the present invention provides a drug delivery device comprising the components described in the first aspect of the present invention.

[0053] In some preferred embodiments of the invention, the drug delivery device further includes a component for administering the antibody against varicella-zoster virus or its antigen-binding fragment or the pharmaceutical composition to the subject, such as a syringe or infusion device.

[0054] The thirteenth aspect of the present invention provides a method for detecting VZV-gE protein for non-diagnostic / therapeutic purposes, the method comprising using an antibody against varicella-zoster virus as described in the first aspect of the present invention or an antigen-binding fragment thereof and / or a pharmaceutical composition as described in the eighth aspect of the present invention.

[0055] Based on common knowledge in the field, the above-mentioned preferred conditions can be combined arbitrarily to obtain various preferred embodiments of the present invention.

[0056] The reagents and raw materials used in this invention are all commercially available.

[0057] The positive and progressive effects of this invention are as follows: the drug of this invention belongs to the category of antibody drugs, which not only meet the treatment needs for VZV, but also the antibody drug of this invention is relatively safe, has fewer side effects, and can be combined with other treatment methods to enhance the treatment effect. Attached Figure Description

[0058] Figure 1 The binding activity of the candidate antibodies selected by bioinformatics analysis in this invention to the VZV gE protein was detected by ELISA.

[0059] Figure 2 The results are from a gradient dilution ELISA binding activity assay of the candidate antibody of this invention.

[0060] Figure 3 The results are from a gradient dilution ELISA binding activity assay of the candidate antibody of this invention.

[0061] Figures 4A-4G This is the result of antibody affinity testing.

[0062] Figure 5 This is the result of the in vitro neutralizing activity assay for the antibody. Detailed Implementation

[0063] In this invention, unless otherwise stated, the scientific and technical terms used herein have the meanings commonly understood by those skilled in the art. Furthermore, the operational steps used herein, such as molecular genetics, nucleic acid chemistry, chemistry, molecular biology, biochemistry, cell culture, microbiology, cell biology, genomics, and recombinant DNA, are all conventional steps widely used in their respective fields. To better understand this invention, definitions and explanations of relevant terms are provided below:

[0064] In this invention, the letters in the amino acid sequence represent single-letter abbreviations of amino acids known in the art, such as those described in J. Biol. Chem, 243, p3558 (1968): alanine: Ala-A, arginine: Arg-R, aspartic acid: Asp-D, cysteine: Cys-C, glutamine: Gln-Q, glutamic acid: Glu-E, histidine: His-H, glycine: Gly-G, asparagine: Asn-N, tyrosine: Tyr-Y, proline: Pro-P, serine: Ser-S, methionine: Met-M, lysine: Lys-K, valine: Val-V, isoleucine: Ile-I, phenylalanine: Phe-F, leucine: Leu-L, tryptophan: Trp-W, threonine: Thr-T.

[0065] In this invention, the amino acid sequences of the light chain and heavy chain variable regions CDR1 and 2 are all shown according to the definition of the Chothia numbering rules, and the amino acid sequence of the light chain and heavy chain variable region CDR3 is obtained according to the Cell Ranger V(D) Jannotation definition. However, it is well known to those skilled in the art that antibody CDRs can be defined in various ways, such as Chothia et al. (1989) Nature 342:877-883, Al-Lazikani et al., “Standard conformations for the canonical structures of immunoglobulins”, Journal of Molecular Biology, 273, 927-948 (1997)), based on antibody sequence variability (Kabat et al., Sequences of Proteins of Immunological Interest, 4th edition, USDepartment of Health and Human Services, National Institutes of Health (1987)), AbM (University of Bath), Contact (University College London), the international ImMunoGeneTics database (IMGT, imgt.cines.fr / ), and Northrop Grumman's method based on affinity propagation clustering using a large number of crystal structures. CDR Definition. Those skilled in the art will understand that, unless otherwise specified, the terms “CDR” and “complementarity-determining region” for a given antibody or its region (e.g., variable region) should be understood to encompass the complementarity-determining region defined as in any of the known embodiments described above by way of the present invention.

[0066] Therefore, when referring to antibodies defined by a specific CDR sequence as defined in this invention, the scope of said antibody also includes antibodies whose variable region sequence contains the specific CDR sequence, but whose claimed CDR boundaries differ from those defined in this invention due to the application of different schemes (e.g., different assignment system rules or combinations). Although the scope of protection claimed in this invention is based on the sequence defined according to the Chothia / Cell Ranger V(D)J annotation numbering rules, amino acid sequences corresponding to other CDR definition rules should also fall within the scope of protection of this invention.

[0067] In this invention, the term "full-length antibody" is used interchangeably to refer to a glycoprotein comprising at least two heavy chains (HC) and two light chains (LC) linked together by disulfide bonds. Each heavy chain consists of a heavy chain variable region (abbreviated as VH in this invention) and a heavy chain constant region. The heavy chain constant region consists of three domains: CH1, CH2, and CH3. Each light chain consists of a light chain variable region (abbreviated as VL in this invention) and a light chain constant region (abbreviated as CL in this invention). The light chain constant region consists of one domain: CL. Mammalian heavy chains are classified as α, δ, ε, γ, and μ. Mammalian light chains are classified as λ or κ. Immunoglobulins containing α, δ, ε, γ, and μ heavy chains are classified as immunoglobulins IgA, IgD, IgE, IgG, and IgM. A complete antibody forms a "Y" shape. The stem of the Y is formed by the second and third constant regions of the two heavy chains (and, for IgE and IgM, a fourth constant region) linked together, and disulfide bonds (interchain) are formed in the hinge. Heavy chains γ, α, and δ have constant regions consisting of three tandem (in a row) Ig domains and hinge regions for increased flexibility; heavy chains μ and ε have constant regions consisting of four immunoglobulin domains. The second and third constant regions are referred to as the "CH2 domain" and the "CH3 domain," respectively. Each arm of Y includes a variable region of a single heavy chain and a first constant region that binds to a variable and constant region of a single light chain. The variable regions of the light and heavy chains are responsible for antigen binding.

[0068] In this invention, a "Fab fragment" consists of a light chain and a heavy chain, comprising the CH1 domain and a variable region. The heavy chain of the Fab molecule cannot form disulfide bonds with another heavy chain molecule. The "Fc" region contains two heavy chain fragments containing the CH2 and CH3 domains of the antibody. The two heavy chain fragments are held together by two or more disulfide bonds and through the hydrophobic interaction of the CH3 domain. A "Fab' fragment" contains a portion of a light chain and a heavy chain containing the VH domain, the CH1 domain, and the region between the CH1 and CH2 domains, thereby allowing interchain disulfide bonds to form between the two heavy chains of the two Fab' fragments to form the F(ab')2 molecule. An "F(ab')2 fragment" contains two light chains and two heavy chains containing portions of the constant region between the CH1 and CH2 domains, thereby forming interchain disulfide bonds between the two heavy chains. Therefore, the F(ab')2 fragment consists of two Fab' fragments held together by disulfide bonds between the two heavy chains. The term "Fv" refers to an antibody fragment consisting of the VL and VH domains of a single arm of the antibody, but lacking the constant region.

[0069] In this invention, scFv refers to a single-chain antibody fragment, which includes a heavy chain variable region, a light chain variable region, and a linker peptide of 15-20 amino acids. The VL and VH domains enable the linker peptides to pair and form monovalent molecules as single polypeptide chains (see, for example, Bird et al., Science 242:423-426 (1988) and Huston et al., Proc. Natl. Acad. Sci. USA 85:5879-5883 (1988)). Such scFv molecules may have a general structure: NH2-VL-linker peptide-VH-COOH or NH2-VH-linker peptide-VL-COOH.

[0070] In this invention, "nucleic acid" refers to a nucleotide chain of any length and includes DNA and RNA. A nucleotide can be a deoxyribonucleotide, ribonucleotide, modified nucleotide or base, and / or its analogues, or any substrate capable of being incorporated into the chain by DNA or RNA polymerase.

[0071] In this invention, the term "recombinant expression vector" refers to a genetically modified oligonucleotide or polynucleotide construct that, when the construct contains a nucleotide sequence encoding mRNA, protein, polypeptide, or peptide, and the vector is contacted with a cell under conditions sufficient to allow the mRNA, protein, polypeptide, or peptide to be expressed in the cell, permits the expression of the mRNA, protein, polypeptide, or peptide by the host cell. The vectors of this invention are generally not naturally occurring. However, portions of the vector may be naturally occurring. The recombinant expression vectors of this invention can contain any type of nucleotide, including but not limited to DNA and RNA that can be single-stranded or double-stranded, synthetic or partially obtained from natural sources, and may contain natural, non-natural, or modified nucleotides. Recombinant expression vectors can contain naturally occurring or non-naturally occurring nucleotide linkages, or both. In an exemplary aspect, modified nucleotides or non-naturally occurring nucleotide linkages do not impede transcription or replication of the vector.

[0072] The recombinant expression vector of the present invention can be any suitable recombinant expression vector capable of being used to transform or transfect one or more genes or sequences of interest into any suitable host cell and preferably to express the genes or sequences in the host cell. Suitable vectors include those designed for amplification and expansion or for expression or both of the above, and examples of vectors include, but are not limited to, viral vectors, naked DNA or RNA expression vectors, plasmids, granules or phage vectors, DNA or RNA expression vectors associated with cationic condensers, DNA or RNA expression vectors encapsulated in liposomes, and certain eukaryotic cells, such as production cells.

[0073] In this invention, the term "host cell" refers to any type of cell that may contain the nucleic acids or vectors described herein. In exemplary aspects, the host cell is a eukaryotic cell, such as a plant, animal, fungus, or algae; or it may be a prokaryotic cell, such as a bacterium or protozoan.

[0074] In this invention, the pharmaceutical composition may comprise a suitable pharmaceutically acceptable carrier, such as pharmaceutical excipients, including buffers, as known in the art. "Pharmaceutically acceptable carrier" includes any and all physiologically compatible solvents, dispersion media, isotonic agents, and absorption delay agents. Water is a preferred carrier when the pharmaceutical composition is administered intravenously. Saline solutions, aqueous dextran, and glycerol solutions can also be used as liquid carriers, particularly for injectable solutions. Pharmaceutical compositions comprising the invention can be prepared by mixing antibodies of the invention having the desired purity with one or more optional pharmaceutical excipients (Remington's Pharmaceutical Sciences, 16th edition, Osol, A. ed. (1980)). Preferably, the composition is in the form of a lyophilized formulation or an aqueous solution.

[0075] The pharmaceutical compositions of the present invention may also comprise more than one active ingredient required for a specific indication to be treated, preferably those active ingredients having complementary activities that do not adversely affect each other. For example, it is desirable to also provide other active ingredients, such as other antibodies, antiviral agents, small molecule drugs, or immunomodulators. The active ingredients are suitably combined in amounts effective for the intended use. Sustained-release formulations can be prepared, suitable examples of which include a semi-permeable matrix of a solid hydrophobic polymer containing the antibody of the present invention, said matrix being a shaped article, such as a film or microcapsule.

[0076] In this invention, the chimeric antigen receptor (CAR) is an engineered transmembrane protein that combines the specificity of an antigen-specific antibody with the function of a T-cell receptor. Generally, a CAR comprises an extracellular domain, a transmembrane domain, and an intracellular domain. In an exemplary aspect, the extracellular domain of the CAR contains an antigen recognition region, which may be a scFV of an antigen-specific antibody.

[0077] In this invention, the term "antibody-drug conjugate" generally refers to an antibody linked to a biologically active cytotoxic agent via a stable linker unit. The "cytotoxic agent" may include toxins such as small molecule toxins or enzyme-active toxins of bacterial, fungal, plant, or animal origin, radioactive isotopes, toxic drugs, chemotherapeutic drugs, antibiotics, or ribolysins, or derivatives thereof.

[0078] In this invention, the application scenarios for "non-diagnostic / therapeutic purposes" include, but are not limited to: for example, detecting the presence or absence of antigen (VZV-gE) in vitro in the laboratory; or using it as a positive antibody to screen other antibodies targeting VZV-gE; or competing with other antibodies targeting VZV-gE to detect whether there is competition between the antibodies, i.e., whether the antigen epitopes are the same or similar.

[0079] The present invention is further illustrated below by way of embodiments, but the invention is not limited to the scope of the embodiments described herein. Experimental methods in the following embodiments that do not specify specific conditions were performed according to conventional methods and conditions, or as selected according to the product instructions.

[0080] Example 1: Enrichment of peripheral blood gE antibody-positive B cells from varicella-zoster patients

[0081] 50 mL of peripheral blood was collected from patients who had recovered from varicella-zoster virus (ZZV) and diluted with an equal volume of PBS. Lymphocyte separation medium (Solarbio, #P8610) was added according to the manufacturer's instructions, and PBMC cells were isolated using density gradient centrifugation. B cells in the PBMCs were then isolated using human CD19 magnetic beads (Miltenyi Biotec, #130-050-301). B cells expressing VZV-gE antibody were then screened by flow cytometry using CD27+ / VZV-gE-flag+ / VZV-gE-Avi+ gating. The enriched positive B cells were counted using a cell counter (Bio-rad TC20), and the cell concentration was adjusted to 1000 cells / μL for subsequent single-cell library construction.

[0082] Example 2: Candidate antibody sequences were obtained through single-cell sequencing and data analysis.

[0083] B cells enriched with VZV-gE antibody in Example 1 were used for single-cell library construction according to the 10x Genomics manual (CG000331). B cells were added to 10x Chromium NextGEM Chip K at the adjusted concentration, and single-cell 5′ expression profiling was performed using a kit (10x Genomics, #1000263) for library construction. V(D)J enrichment of B cells was performed using a kit (10×Genomics, #1000253). SPRI magnetic beads (Beckman Coulter, #B23318) were used for cDNA purification and size selection during library construction. Qubit 4.0 was used to quantify cDNA amplification products, targeted enrichment, and completed library products. The size distribution of cDNA products and the final product was detected using a high-sensitivity chip in a 2100 biochemical analyzer (Agilent, #50674626). After library construction, paired-end sequencing (150 bp) was performed using an Illumina sequencing platform. Each mRNA library was sequenced at 120G, and each BCR library was sequenced at 20G.

[0084] After standard sequencing quality control, single-cell transcriptome data were analyzed using software such as Cellranger (v6.1.2), Seurat (v4.0.3), and Scrublet (v0.2.1) to predict the blood cell type of each cell. Scanpy (v1.5.1) was used to filter single cells from all samples, retaining those with a total gene count greater than 400, a total UMI count greater than 800, and a mitochondrial gene ratio less than 0.15. These cells were then standardized, logized, normalized, and highly variable genes were identified. Scanpy (v1.5.1) was used to de-batch correct and perform single-cell clustering on the processed expression matrix. Finally, UMAP was used to visualize the cell clustering results. By combining the blood cell type mapping results with the cell population-specific highly expressed signaling genes (CD27 and GPR183), memory B cells were precisely defined. After standard sequencing quality control, single-cell BCR data were processed using the VDJ function of Cellranger (v6.1.2) software to obtain the contiguous group sequence and annotation information for each heavy or light chain. High-confidence, producible heavy or light chains with a UMI greater than or equal to 2 were retained. The heavy and light chains contained in each cell were integrated based on the cell ID. The size of each clone was calculated, and the heavy / light chain genes and sequences of that clone, the cell IDs of the cells it contained, and the average UMI number of the cells it contained were saved. By determining whether the amino acid and base sequences of the heavy / light chains were consistent, antibody sequences from all samples were integrated, and the clone size was output. Antibody sequences with a frequency of 1 or higher were used for subsequent analysis. The mismatch number of each antibody sequence was obtained using Igblast (v1.18.0) software based on the VDJ region of the heavy chain, and the somatic hypermutation rate (SHM) of each antibody sequence was calculated based on the mismatch number. This was integrated with cell annotation information from single-cell transcriptomics, and antibody sequences with a frequency greater than or equal to 1 underwent deep filtering: sequences containing B cells expressing IGHG1, sequences not containing B cells expressing IGHG2, sequences containing memory B cells, and sequences with a somatic hypermutation rate greater than 0.02. After deep filtering, 53 antibody heavy chain and light chain variable region sequences were obtained for subsequent screening experiments.

[0085] Example 3: Transient expression and binding activity assay of candidate antibodies in HEK293 cells

[0086] The heavy chain variable region genes of the 53 pairs of antibodies screened by bioinformatics analysis in Example 2 were ligated into pcDNA3.4 vectors containing the human IgG1 constant region, and the light chain variable regions were ligated into PCDNA3.4 vectors corresponding to lambda or kappa, to construct expression plasmids for fully human neutralizing antibodies against varicella-zoster virus. The recombinant plasmids of the heavy and light chains obtained from the same cell were mixed with transfection reagent PEI 25000 (MKBio, #MX2202) (ratio 1:3) and co-transfected into HEK293 cells. The cells were cultured at 37°C with 5% CO2 and a shaker speed of 120 rpm. After 5 days, 200 μL of culture supernatant was collected, and the binding activity against VZV gE protein was detected by ELISA. The results of the binding activity experiment are shown in […]. Figure 1 The negative control was Anti-HEL-HumanIgG1 Isotype-control (Biointron, #B117901); the amino acid sequence of the heavy chain variable region of the positive control antibody is shown in SEQ ID NO:61, and the amino acid sequence of the light chain variable region is shown in SEQ ID NO:62. The heavy chain constant region of the positive control antibody is derived from the human IgG1 heavy chain constant region, and the light chain constant region is derived from the kappa type light chain constant region.

[0087] Figure 1 The heavy chain variable region sequence (SEQ ID NO:61) of the positive control antibody used is as follows:

[0088] MAVLGLLFCLVTFPSCVLSQVQLKQSGPGLVQPSQSLSITCTVSGFSLTTYGVHWVRQSPGEGLEWLGVIWSGGSTDYNAAFISRLSISKDNSKSQVFFKMNSLQANDTAIYFCARKEYGHYRNAMDYWGQGTSITVSS

[0089] Figure 1 The light chain variable region sequence (SEQ ID NO:62) of the positive control antibody used is as follows:

[0090] MKLPVRLLLVLMFWIPASSSDVVMTQTPLSLPVSLGDQASISCRSSQSLVHSNGNTYLHWYLQKPGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYFCSQSTHVPFTFGSGTKLEIK

[0091] Select antibodies with high binding activity and then perform serial dilutions to calculate their EC50. 50Value (calculated based on the antibody's molecular weight of 144 kDa, 100 nM = 14.4 μg / mL), results of gradient dilution binding activity assays are shown below. Figure 2 , Figure 3 The calculated EC 50 The values ​​are shown in Tables 1 and 2 below.

[0092] Table 1 Figure 2 EC corresponding to the antibody 50 value

[0093]

[0094]

[0095] Table 2 Figure 3 EC corresponding to the antibody 50 value

[0096]

[0097] The ELISA procedure is as follows: VZV-gE-his protein 2 μg / mL, 100 μL / well, coated overnight at 4℃, washed 5 times, and blotted dry; 5% skim milk (PBS), 200 μL / well, incubated at 25℃ for 1 h, washed 5 times, and blotted dry; 100 nM supernatant, 100 μL / well, duplicate wells, if less than 100 nM, add 100 μL stock solution, incubated at 25℃ for 1 h, washed 5 times, and blotted dry; Secondary antibody: Anti-human IgG Fc HRP (Abcam, #ab99759), diluted 1:10000 with PBS, 100 μL / well, incubated at 25℃ for 1 h, washed 5 times, and blotted dry; Color development: 100 μL / well color development solution, incubated at room temperature in the dark for 3.5 min; Termination: 50 μL / well stop solution; Reading: OD450, wells with a colorimetric value of 0.5 or higher are considered positive.

[0098] The sequence (SEQ ID NO:63) of the VZV-gE-his protein used in the ELISA experiment is as follows:

[0099] MGTVNKPVVGVLMGFGIITGTLRITNPVRASVLRYDDFHIDEDKLDTNSVYEPYYHSDHAESSWVNRGESSRKAYDHNSPYIWPRNDYDGFLENAHEHHGVYNQGRGIDSGERLMQPTQMSAQEDLGDDTGIHVIPTLNG DDRHKIVNVDQRQYGDVFKGDLNPKPQGQRLIEVSVEENHPFTLRAPIQRIYGVRYTETWSFLPSLTCTGDAAPAIQHICLKHTTCFQDVVVDVDCAENTKEDQLAEISYRFQGKKEADQPWIVVNTSTLFDELELDPPE IEPGVLKVLRTEKQYLGVYIWNMRGSDGTSTYATFLVTWKGDEKTRNPTPAVTPQPRGAEFHMWNYHSHVFSVGDTFSLAMHLQYKIHEAPFDLLLEWLYVPIDPTCQPMRLYSTCLYHPNAPQCLSHMNSGCTFTSPHL AQRVASTVYQNCEHADNYTAYCLGISHMEPSFGLILHDGGTTLKFVDTPESLSGLYVFVVYFNGHVEAVAYTVVSTVDHFVNAIEERGFPPTAGQPPATTKPKEITPVNPGTSPLLRGSGSDYKDDDDKAAAHHHHHHHH

[0100] Serial dilution ELISA: VZV-gE-His protein 2 μg / mL, 100 μL / well, incubate overnight at 4°C, wash 5 times, blot dry; blocking buffer 200 μL / well, incubate at 25°C for 1 h, wash 5 times, blot dry; add antibody to be tested, starting with 100 nM in the first well, 4-fold serial dilution, 8 serial dilutions, 100 μL / well, incubate at 25°C for 1 h, wash 5 times, blot dry; secondary antibody: Anti-human IgG Fc HRP (Abcam, #ab99759) diluted 1:10000 with PBS, 100 μL / well, incubate at 25°C for 1 h, wash 5 times, blot dry; color development: 100 μL / well color development solution, incubate at room temperature in the dark for 3.5 min; stop: 50 μL / well stop solution; reading: OD450.

[0101] Example 4: Large-scale expression and purification of recombinant antibodies

[0102] Of the 53 antibodies, 7 showed high binding affinity (OD450>2) to VZV-gE protein in their culture supernatants, and EC... 50The value can reach below 0.5 nM. Seven antibodies with high binding activity were selected for large-scale expression and purification. The method was the same as above. After culturing for 5 days, the culture supernatant was collected by centrifugation at 6000 rpm for 15 min at 4℃. The supernatant was purified by affinity chromatography in protein A medium (GenScript, #L00210). The purified antibody was identified by SDS-PAGE and used in subsequent experiments.

[0103] The sequence information of the CDR, heavy chain variable region, and light chain variable region of the seven antibodies with high binding capacity to VZV-gE obtained by screening is shown in the table below:

[0104] Table 3. CDR sequences of antibodies with high binding affinity obtained through screening.

[0105]

[0106]

[0107] The CDR sequences of the heavy chain variable region and light chain variable region of the aforementioned antibodies WLL-1 and WLL-25 are very similar. The present invention summarizes their CDR sequences as follows:

[0108] GFSLX1X2X3X4M (SEQ ID NO:42); where X1 is T or S; X2 is N or T; X3 is T or A; and X4 is E or G.

[0109] X5WDDX6 (SEQ ID NO:43); where X5 is Y or D; X6 is D or S.

[0110] CARX7X8X9X 10 X 11 LX 12 X 13 DYW (SEQ ID NO:44); where X7 is L or T; X8 is S or M; X9 is L or Y; X 10 For R or Q; X 11 For L or F; X 12 For T or G; X 13 It can be L or F.

[0111] GGX 14 NIGSKSVH (SEQ ID NO:45); where X 14 It can be S or N.

[0112] CQVWDX 15 X 16 X 17 DHPVF (SEQ ID NO:46); where X 15 For T or S; X 16 For S or G; X17 For G or S.

[0113] Table 4. Sequences of the heavy chain and light chain variable regions of the high-binding antibodies obtained through screening.

[0114]

[0115]

[0116] The constant region information of the seven antibodies is shown in Table 5 below.

[0117] Table 5. Constant region subtypes of antibodies with high binding capacity obtained through screening.

[0118] serial number Heavy chain constant region (human) Light chain constant region (human) WLL-1 Human IgG1 lambda WLL-15 Human IgG1 lambda WLL-18 Human IgG1 kappa WLL-19 Human IgG1 lambda WLL-25 Human IgG1 lambda WLL-28 Human IgG1 kappa WLL-30 Human IgG1 lambda

[0119] Example 5: Affinity Detection of Recombinant Antibodies

[0120] The KD value of the antigen protein and the antibody of this invention was detected using surface plasmon resonance (SPR) technology (Biacore T200 instrument). The antigen protein was coupled to a CM5 chip via amino-coupling using an amino-coupling kit (Cytiva, #BR-1000-50) and a coupling buffer of 10 mM sodium acetate at pH 4.0 (Cytiva, #BR-1003-49). The antigen VZV-gE-his was used as a ligand for coupling. Seven antibody strains were serially diluted as analytes using a buffer (0.01 M HEPES, 0.15 M NaCl, 3 mM EDTA, 0.08% P2O, pH 7.4). The binding time was 200 s, the dissociation time was 1200 s, and one channel was used as a reference channel.

[0121] Table 6. Antibody Concentrations at Serial Dilutions

[0122] WLL-1 WLL-15 WLL-18 WLL-19 WLL-25 WLL-28 WLL-30 12.5nM 25nM 200nM 400nM 400nM 25nM 100nM 6.25nM 12.5nM 100nM 200nM 200nM 12.5nM 50nM 3.125nM 6.25nM 50nM 100nM 100nM 6.25nM 25nM 1.5625nM 3.125nM 25nM 50nM 50nM 3.125nM 12.5nM 0.78125nM 1.5625nM 12.5nM 25nM 25nM 1.5625nM 3.125nM 0.390625nM 0.78125nM 6.25nM 12.5nM 12.5nM 0.78125nM 0.78125nM

[0123] Use Biacore TM Insight Evaluation Software fitted the data using a 1:1 assortment model, and the results are as follows: Figures 4A-4G As shown in Table 7, all seven antibodies of the present invention possess good antigen affinity.

[0124] Table 7. KD values ​​of 7 antibodies and antigen VZV-gE-his protein

[0125]

[0126]

[0127] Example 6: Detection of in vitro neutralizing activity of recombinant antibodies

[0128] The neutralizing activity of antibodies was detected using human embryonic lung fibroblasts MRC-5 (ATCC, #CCL-171) and Oka strain (ATCC, #VR-1832). Neutralizing antibodies neutralize VZV's ability to infect cells. Upon entering cells, VZV expresses virus-specific proteins. Green fluorescent antibody (Anti-VZV-gE-rHmAb(488Conjugated); Vazyme, #ABA0151J) was used to identify viruses with infective and replicative capabilities. The IC50 was calculated by comparing the amount of infective virus with that of the VZV control group. 50 (The concentration of the test substance when VZV virus is 50% inhibited) indicates the magnitude of the test substance's neutralizing activity against VZV virus. The experimental procedure is as follows:

[0129] 1. Cell preparation: Adjust the concentration of MRC-5 cell suspension, seed into 96-well plates, and incubate overnight in a cell culture incubator (37℃, 5% CO2). Ensure that the cell confluence is about 90% on the second day before starting the experiment.

[0130] 2. Serum inactivation: Inactivate in a water bath at 56°C for 30 minutes (antibodies do not need to be inactivated).

[0131] 3. Serial dilution: The initial concentration of the 7 antibody strains to be tested in this invention was 800 μg / mL in the first well using dilution buffer containing guinea pig complement (Solarbio, #S4990). Serial dilutions were performed in 5-fold serial dilutions, resulting in a total of 12 dilutions (including the initial well) and 2 replicates.

[0132] 4. Virus dilution: Based on the PFU value of the virus, dilute the virus with a fluorescent area of ​​5000-15000 using a diluent containing guinea pig complement.

[0133] 5. Neutralization reaction: Add diluted virus to the sample wells and virus control wells respectively, and incubate at 37°C and 5% CO2 for about 1 hour for neutralization.

[0134] 6. Virus adsorption: Add 50 μL of the virus and antibody neutralization product to each MRC-5 cell culture well, with two replicates. Incubate at 37°C in a 5% CO2 incubator for about 2 hours. Change the medium and add 100 μL of culture medium to each well and continue incubation for about 48 hours.

[0135] 7. Plate preparation: Discard the supernatant, fix the cells, add fluorescently labeled detection antibody, and read the plate using a CTL (S6 Ultra M2) instrument.

[0136] The results are as follows Figure 5 As shown, all seven antibodies of the present invention possess good VZV virus neutralizing activity.

[0137] While specific embodiments of the present invention have been described above, those skilled in the art should understand that these are merely illustrative examples, and various changes or modifications can be made to these embodiments without departing from the principles and essence of the present invention. Therefore, the scope of protection of the present invention is defined by the appended claims.

Claims

1. An antibody or antigen-binding fragment thereof against varicella-zoster virus, characterized in that, The antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 having the amino acid sequences set forth in SEQ ID NOs: 42, 43, and 44, respectively; and a light chain variable region comprising LCDR1, LCDR2, and LCDR3 having the amino acid sequences set forth in SEQ ID NOs: 45, 5, and 46, respectively; or, The heavy chain variable region comprises HCDR1, HCDR2, and HCDR3 having the amino acid sequences set forth in SEQ ID NOs: 7, 8, and 9, respectively; and the light chain variable region comprises LCDR1, LCDR2, and LCDR3 having the amino acid sequences set forth in SEQ ID NOs: 10, 11, and 12, respectively; or, The heavy chain variable region comprises HCDR1, HCDR2, and HCDR3 having the amino acid sequences set forth in SEQ ID NOs: 13, 14, and 15, respectively; and the light chain variable region comprises LCDR1, LCDR2, and LCDR3 having the amino acid sequences set forth in SEQ ID NOs: 16, 17, and 18, respectively; or, The heavy chain variable region comprises HCDR1, HCDR2, and HCDR3 having the amino acid sequences set forth in SEQ ID NOs: 19, 20, and 21, respectively; and the light chain variable region comprises LCDR1, LCDR2, and LCDR3 having the amino acid sequences set forth in SEQ ID NOs: 22, 23, and 24, respectively; or, The heavy chain variable region comprises HCDR1, HCDR2, and HCDR3 having the amino acid sequences set forth in SEQ ID NOs: 30, 31, and 32, respectively; and the light chain variable region comprises LCDR1, LCDR2, and LCDR3 having the amino acid sequences set forth in SEQ ID NOs: 33, 34, and 35, respectively; or, The heavy chain variable region comprises HCDR1, HCDR2, and HCDR3 having the amino acid sequences set forth in SEQ ID NOs: 36, 37, and 38, respectively; and the light chain variable region comprises LCDR1, LCDR2, and LCDR3 having the amino acid sequences set forth in SEQ ID NOs: 39, 40, and 41, respectively.

2. The anti-varicella-zoster virus antibody or antigen-binding fragment thereof of claim 1, wherein, The heavy chain variable region comprises HCDR1, HCDR2, and HCDR3 having the amino acid sequences set forth in SEQ ID NOs: 1, 2, and 3, respectively; and the light chain variable region comprises LCDR1, LCDR2, and LCDR3 having the amino acid sequences set forth in SEQ ID NOs: 4, 5, and 6, respectively; or, The heavy chain variable region comprises HCDR1, HCDR2, and HCDR3 having the amino acid sequences set forth in SEQ ID NOs: 25, 26, and 27, respectively; and the light chain variable region comprises LCDR1, LCDR2, and LCDR3 having the amino acid sequences set forth in SEQ ID NOs: 28, 5, and 29, respectively.

3. The anti-varicella-zoster virus antibody or antigen-binding fragment thereof of claim 1, wherein, the framework region of the heavy chain variable region and / or the light chain variable region is a human framework region; Preferably, the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 47 or at least 80% identity to the amino acid sequence as set forth in SEQ ID NO: 47; and / or, the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 48 or at least 80% identity to the amino acid sequence as set forth in SEQ ID NO: 48; or, the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 49 or at least 80% identity to the amino acid sequence as set forth in SEQ ID NO: 49; and / or, the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 50 or at least 80% identity to the amino acid sequence as set forth in SEQ ID NO: 50; or, the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 51 or at least 80% identity to the amino acid sequence as set forth in SEQ ID NO: 51; and / or, the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 52 or at least 80% identity to the amino acid sequence as set forth in SEQ ID NO: 52; or, the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 53 or at least 80% identity to the amino acid sequence as set forth in SEQ ID NO: 53; and / or, the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 54 or at least 80% identity to the amino acid sequence as set forth in SEQ ID NO: 54; or, the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 55 or at least 80% identity to the amino acid sequence as set forth in SEQ ID NO: 55; and / or, the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 56 or at least 80% identity to the amino acid sequence as set forth in SEQ ID NO: 56; or, the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 57 or at least 80% identity to the amino acid sequence as set forth in SEQ ID NO: 57; and / or, the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 58 or at least 80% identity to the amino acid sequence as set forth in SEQ ID NO: 58; or, the heavy chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 59 or at least 80% identity to the amino acid sequence as set forth in SEQ ID NO: 59; and / or, the light chain variable region comprises an amino acid sequence as set forth in SEQ ID NO: 60 or at least 80% identity to the amino acid sequence as set forth in SEQ ID NO:

60.

4. The anti-varicella-zoster virus antibody or antigen-binding fragment thereof of any one of claims 1-3, wherein, The anti-varicella-zoster virus antibody or antigen-binding fragment thereof is any one of the following antibody forms: (a) a full-length antibody; (b) an scFv; (c) a fusion protein comprising an scFv; (d) a Fab fragment; (e) a Fab' fragment; and, (f) a F(ab)2; Alternatively, the anti-varicella-zoster virus antibody or antigen-binding fragment thereof is a monoclonal antibody or a polyclonal antibody; Alternatively, the anti-varicella-zoster virus antibody or antigen-binding fragment thereof is a humanized antibody and / or a bispecific antibody. Preferably, the antibody or antigen-binding fragment thereof is a full-length antibody, whose heavy chain constant region and / or light chain constant region is derived from a human antibody. More preferably, the heavy chain constant region is derived from a human IgG1 constant region; and / or, the light chain constant region is derived from a human light chain kappa chain constant region or lambda chain constant region.

5. A chimeric antigen receptor, characterized in that, It comprises the anti-varicella-zoster virus antibody or antigen-binding fragment thereof according to any one of claims 1-4.

6. An isolated nucleic acid encoding the anti-varicella-zoster virus antibody or antigen-binding fragment thereof according to any one of claims 1-4, or the chimeric antigen receptor according to claim 5.

7. A recombinant expression vector, characterized in that, The recombinant expression vector comprises the nucleic acid according to claim 6; Preferably, the recombinant expression vector is a plasmid, a cosmid, a bacteriophage or a viral vector; More preferably, the viral vector is a baculovirus vector, a retrovirus vector, a lentivirus vector, an adenovirus vector or an adeno-associated virus vector; the backbone of the plasmid is pcDNA3.

4.

8. A transformant characterized in that, The transformant comprises the recombinant expression vector according to claim 7 in a host cell; Preferably, the host cell is a prokaryotic cell or a eukaryotic cell; More preferably, the host cell is selected from a yeast cell, an insect cell, a mammalian cell or other cells suitable for antibody production; the mammalian cell is, for example, a HEK293 cell.

9. A method of making an antibody or antigen-binding fragment thereof against varicella-zoster virus, characterized in that, It comprises culturing the transformant according to claim 8 to obtain the anti-varicella-zoster virus antibody or antigen-binding fragment thereof from the culture.

10. An antibody drug conjugate, characterized in that, The antibody drug conjugate comprises a cytotoxic agent and the anti-varicella-zoster virus antibody or antigen-binding fragment thereof according to any one of claims 1-4.

11. A pharmaceutical composition, characterized by, The pharmaceutical composition comprises the anti-varicella-zoster virus antibody or antigen-binding fragment thereof according to any one of claims 1-4, the chimeric antigen receptor according to claim 5 or the antibody drug conjugate according to claim 10, and a pharmaceutically acceptable carrier.

12. Use of the anti-varicella-zoster virus antibody or antigen-binding fragment thereof according to any one of claims 1-4, the chimeric antigen receptor according to claim 5, the nucleic acid according to claim 6, the recombinant expression vector according to claim 7, the transformant according to claim 8, the antibody drug conjugate according to claim 10 or the pharmaceutical composition according to claim 11 in the preparation of a medicament for preventing or treating varicella-zoster.

13. A kit characterized in that, The kit comprises the antibody or antigen-binding fragment thereof against varicella-zoster virus as claimed in any one of claims 1 to 4, the chimeric antigen receptor as claimed in claim 5, the antibody-drug conjugate as claimed in claim 10 or the pharmaceutical composition as claimed in claim 11.

14. A kit, characterized in that The kit-of-parts comprises a kit A and a kit B, wherein, The kit A comprises the antibody or antigen-binding fragment thereof as claimed in any one of claims 1 to 4 and / or the pharmaceutical composition as claimed in claim 11; The kit B comprises a further pharmaceutical composition for the prevention or treatment of varicella-zoster and / or a further drug for the prevention or treatment of varicella-zoster.

15. A drug delivery device characterized in that, The administration device comprises the antibody or antigen-binding fragment thereof as claimed in any one of claims 1 to 4 and / or the pharmaceutical composition as claimed in claim 11. Preferably, the administration device further comprises means for administering the antibody or antigen-binding fragment thereof or the pharmaceutical composition to a subject, such as a syringe or an infusion device.

16. A method of detecting VZV-gE protein for non-diagnostic / therapeutic purposes, characterized by, The method comprises the use of the antibody or antigen-binding fragment thereof as claimed in any one of claims 1 to 4 and / or the pharmaceutical composition as claimed in claim 11.

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