Meningococcus outer membrane protein synthetic peptide and application thereof

Abstract

The invention relates to the technical field of biological medicine, in particular to a meningococcus outer membrane protein synthetic peptide and application thereof. The invention discloses a meningococcus outer membrane protein synthetic peptide and application thereof. The amino acid sequence of the polypeptide is at least one of (I)-(IV): (I) an amino acid sequence shown as SEQ ID NO.1; (II) an amino acid sequence as shown in SEQ ID NO. 2; (III) an amino acid sequence as shown in SEQ ID NO.3; (IV) an amino acid sequence as shown in SEQ ID NO.4; the invention discloses a meningococcal outer membrane protein synthetic peptide and an application thereof, and discloses a polypeptide sequence, and a vaccine prepared from the polypeptide or a polymer thereof can effectively deal with the diversity of meningococcal PorA and PorB antigens, is easy to synthesize on a large scale, and has a good application prospect.

Description

Technical Field

[0001] The present application relates to the technical field of biomedicine, and in particular to a synthetic peptide of meningococcal outer membrane protein and its application. Background Art

[0002] Meningococcus is the main cause of epidemic cerebrospinal meningitis (EMM) and fulminant septicemia, and is the only pathogen that can cause MMS. There are 13 different serogroups of meningococci, of which A, B, C, Y and W135 are the main pathogenic groups.

[0003] At present, a variety of membrane components and extracellular components are used in the development of meningococcal vaccines, including class 1, 2 and 3 outer membrane proteins (porin proteins), class 4 outer membrane proteins (Rmp proteins) and class 5 outer membrane proteins (Opacity proteins). PorA protein is a class P1 outer membrane protein, and PorB protein is a class P2 or P3 outer membrane protein. Neisseria meningitidis expresses both types of proteins. PorA and PorB are key antigens that have been used in vaccine preparations and are considered to be ideal antigens for eliciting effective bactericidal antibodies. However, meningococci effectively evade immune responses through antigenicity and phase variation. For example, the secondary structures of PorA and PorB proteins show that both have 8 exposed loop structures (loop I to VIII). Among them, loop I and IV are the variable regions of PorA, while loop I, V, VI and VII are the variable regions of PorB. The antigenic determinants that determine the serosubtype and serotype of the strain mainly exist in the variable regions of the two. The highly immunogenic surface loops of PorA and PorB are primarily responsible for eliciting a less than broadly protective immune response, such that Por proteins derived from a particular meningococcal strain tend to provide immunity preferentially against that particular strain.

[0004] Therefore, in order to effectively deal with the antigenic diversity of meningococcal PorA and PorB, it is crucial to develop novel peptides for synthesizing meningococcal outer membrane protein synthetic peptide vaccines. Summary of the invention

[0005] In view of the deficiencies in the prior art, the present application provides a synthetic peptide of meningococcal outer membrane protein and its application, specifically a polypeptide or its polypeptide polymer for use in a synthetic peptide vaccine of meningococcal outer membrane protein, as well as a vaccine containing the polypeptide or its polypeptide polymer and the application of the vaccine.

[0006] The present application discloses a synthetic peptide of meningococcal outer membrane protein and its application. The vaccine made of the polypeptide or its polymer can effectively deal with the diversity of meningococcal PorA and PorB antigens, is easy to synthesize on a large scale, and has good application prospects.

[0007] In the first aspect, the present application provides a polypeptide, using the following technical solution: The present application analyzes the protein sequences of eleven domestic group B meningococcal strains, studies the variation of porA and porB antigenic sites, and simultaneously combines computer-assisted methods to analyze and predict porA and porB antigenic sites, and obtains conservative antigenic site polypeptide sequences, wherein the amino acid sequence of the polypeptide is at least one of (I) to (IV): (I) the amino acid sequence shown in SEQ ID NO.1; (II) the amino acid sequence shown in SEQ ID NO.2; (III) the amino acid sequence shown in SEQ ID NO.3; (IV) the amino acid sequence shown in SEQ ID NO.4; (V) a sequence having at least 90% homology to the sequence described in (I) to (IV); (VI) An amino acid sequence obtained by substituting, deleting or adding one or two amino acid sequences to the amino acid sequence shown in any one of (I) to (V), and having the same or similar functions as the amino acid sequences shown in (I) to (V).

[0008] More preferably, the amino acid sequence of the polypeptide is the sequence shown in SEQ ID NO.1-4.

[0009] In a second aspect, the present application provides a polypeptide polymer, which adopts the following technical solution: A polypeptide polymer, comprising a polypeptide; the amino acid sequence of the polypeptide is at least one of (I) to (IV): (I) the amino acid sequence shown in SEQ ID NO.1; (II) the amino acid sequence shown in SEQ ID NO.2; (III) the amino acid sequence shown in SEQ ID NO.3; (IV) the amino acid sequence shown in SEQ ID NO.4; (V) a sequence having at least 90% homology to the sequence described in (I) to (IV); (VI) An amino acid sequence obtained by substituting, deleting or adding one or two amino acid sequences to the amino acid sequence shown in any one of (I) to (V), and having the same or similar functions as the amino acid sequences shown in (I) to (V).

[0010] More preferably, the amino acid sequence of the polypeptide is the sequence shown in SEQ ID NO.1-4.

[0011] Preferably, a carrier protein is also included.

[0012] Preferably, the carrier protein comprises at least one of albumin, porin, diphtheria toxin, tetanus toxin, heat-labile enterotoxin and ferritin.

[0013] In a third aspect, the present application provides an application of a polypeptide or a polypeptide polymer in the preparation of a synthetic peptide vaccine of meningococcal outer membrane protein, using the following technical solution: Application of the above polypeptide or the above polypeptide polymer in the preparation of meningococcal outer membrane protein synthetic peptide vaccine.

[0014] In a fourth aspect, the present application provides a synthetic peptide vaccine of meningococcal outer membrane protein, which adopts the following technical scheme: A synthetic peptide vaccine of meningococcal outer membrane protein comprises the above polypeptide or the above polypeptide polymer.

[0015] Preferably, the vaccine further comprises an immune adjuvant.

[0016] Further preferably, the immune adjuvant includes at least one of aluminum adjuvant, squalene, tocopherol, MPL, LPA, CpG and QS-21.

[0017] In a fifth aspect, the present application provides a method for preparing a polypeptide, using the following technical solution: A method for preparing a polypeptide, the preparation method comprises the following steps: Using the resin as a starting material, in the presence of a basic agent, an amino acid constituting the C-terminus of the peptide having an α-amino protecting group is connected to the resin; Remove the protecting group with a decapping agent; The amino acids constituting the peptide are connected in sequence from the C-terminus to the N-terminus of the peptide to react, thereby forming a peptide-connected resin, and then the peptide is cleaved and the crude product is purified to obtain a polypeptide.

[0018] In a specific embodiment, a method for preparing a polypeptide comprises the following steps: (1) Deprotection reaction: react in a 15% to 30% by volume solution of hexahydropyridine in N-methylpyrrolidone at 20-28°C for 25-40 minutes to remove the 9-fluorenylmethoxycarbonyl protecting group on the amino group of the resin, blow dry with nitrogen, and wash with N-methylpyrrolidone; (2) Activation of amino acids: reacting the amino acids with 9-fluorenylmethoxycarbonyl protecting groups used in the synthesis with 1-hydroxybenzotriazole to synthesize amino acid-1-hydroxybenzotriazole esters; (3) Condensation reaction: Use a peptide synthesizer to automatically add the above-mentioned various amino acids, resins and diisopropylcarbodiimide to the reactor, react at 20-28°C for 0.5-2.5 hours, blow dry with nitrogen, and wash the resin with N-methylpyrrolidone; (4) Acetylation reaction: using 1.5%-4% (g / mL) acetylimidazole N-methylpyrrolidone solution by weight volume percentage to react with the resin obtained in step (3) at 20-28° C. for 20-40 minutes, drying with nitrogen, and washing the resin with methanol; (5) The synthesis process is repeated from the C-terminus to the N-terminus according to the amino acid sequence. After the reaction is completed, it is washed with N-methylpyrrolidone to obtain a dry polypeptide resin; (6) Separation of polypeptide and resin: Add cleavage reagent to the dried polypeptide resin, stir at a constant speed for 1-4 hours, then place at 0°C for 10 minutes, return to room temperature, evaporate trifluoroacetic acid, add tert-butyl methyl ether and diethyl ether to the polypeptide solution, stir and wash, and filter to obtain the polypeptide solution; (7) Ultrafiltration purification of polypeptides and aseptic treatment: Use membrane packages to ultrafilter polypeptides at 20-28°C and use a 0.22 μm online filter for sterilization and storage.

[0019] Preferably, the cleavage reagent comprises trifluoroacetic acid, triisopropylsilane, ethanedithiol, phenol and water; the volume ratio of the trifluoroacetic acid, triisopropylsilane, ethanedithiol, phenol and water is 85:8:3:3:1.

[0020] In a sixth aspect, the present application provides a method for preparing a polypeptide polymer, using the following technical solution: A method for preparing a polypeptide polymer, the preparation method comprises the following steps: After activating the carrier protein with 4-(N-maleimidomethyl)cyclohexane-1-carboxylic acid 3-sulfo-N-hydroxysuccinimide ester sodium salt, filtering and desalting to obtain the activated carrier protein; Mixing the polypeptide sequences in equal proportions to obtain a polypeptide mixture; The polypeptide mixture is coupled with the activated carrier protein to obtain a polypeptide polymer.

[0021] Preferably, the mass ratio of the sodium salt of 4-(N-maleimidomethyl)cyclohexane-1-carboxylic acid 3-sulfo-N-hydroxysuccinimide ester to the carrier protein is (0.5-1):(3-7).

[0022] Preferably, the volume mass ratio of the polypeptide mixture to the activated carrier protein is (0.1-1) mL: (4-8) mg.

[0023] The present application designs a conservative PorA protein polypeptide so that the immune response is mainly directed against the conservative epitope, and enhances the immunogenicity of the synthetic polypeptide by coupling it to a carrier protein carrier, so that the vaccine containing the synthetic polypeptide provides a broader spectrum of immune protection against Neisseria meningitidis strains.

[0024] In a seventh aspect, the present application provides an application of a synthetic peptide vaccine of meningococcal outer membrane protein, using the following technical solution: An application of a synthetic peptide vaccine of meningococcal outer membrane protein, the application comprising at least one of the following: (1) Use in the preparation of drugs for preventing and / or treating diseases caused by meningococci; (2) Use in the preparation of drugs for preventing and / or treating epidemic cerebrospinal meningitis; (3) Use in the preparation of drugs for preventing and / or treating fulminant sepsis.

[0025] In summary, the present application includes at least one of the following beneficial technical effects: The present application discloses a synthetic peptide of meningococcal outer membrane protein and its application, and discloses a polypeptide sequence. A vaccine made from the polypeptide or its polymer can effectively deal with the diversity of meningococcal PorA and PorB antigens, is easy to synthesize on a large scale, and has good application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 This is the result diagram of ELISA testing of antigen-specific serum IgG; Figure 2 This is the result of ELISA detection of antigen-specific secretory IgA. DETAILED DESCRIPTION

[0027] The experimental methods in the following examples of this application without specifying specific conditions are usually carried out under conventional conditions or under conditions recommended by the manufacturer; the experimental materials and reagents involved in the following contents are commercially available unless otherwise specified.

[0028] Unless otherwise defined, all technical and scientific terms used in this application have the same meaning as those commonly understood by those skilled in the art to which this application belongs. The terms used in the specification of this application are only for the purpose of describing specific embodiments and are not intended to limit this application.

[0029] The terms "including" and "having" and any variations thereof in this application are intended to cover non-exclusive inclusions. For example, a process, method, device, product or equipment comprising a series of steps is not limited to the listed steps or modules, but may optionally include steps not listed, or may optionally include other steps inherent to these processes, methods, products or equipment.

[0030] The following will be combined with specific embodiments to clearly and completely describe the technical solution of this application. Obviously, the described embodiments are only part of the embodiments of this application, not all of them. Based on the embodiments in this application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0031] Example 1: Solid Phase Synthesis of Meningococcal Outer Membrane Protein Synthetic Peptide Vaccine Polypeptide Antigen This example adopts the Merrifield solid phase synthesis method, the solid phase carrier is Rink Amide MBHA resin, and the instrument is ABI 433A fully automatic peptide synthesizer.

[0032] 1. Preparation of synthetic raw materials: The sequences of the meningococcal outer membrane protein synthetic peptide vaccine polypeptides are the amino acid sequence shown in SEQ ID NO.1, the amino acid sequence shown in SEQ ID NO.2, the amino acid sequence shown in SEQ ID NO.3, and the amino acid sequence shown in SEQ ID NO.4.

[0033] Prepare appropriate 9-fluorenylmethoxycarbonyl (Fmoc)-modified amino acids according to the above polypeptide antigen sequence and the synthesis scale of 1 mmol, and add them to the corresponding Cartridge (small bottle containing amino acids). Similarly, weigh the Rink AmideMBHA resin as required, put it into the reaction chamber, and install the reaction chamber into the synthesizer. Place N-methylpyrrolidone (NMP), hexanoyl imidazole (AIM), piperidine (PIP), methanol, etc. in the corresponding reagent bottles.

[0034] 2. Preparation of synthetic peptides of meningococcal outer membrane protein: (1) Deprotection reaction: react in a 15% to 30% by volume solution of hexahydropyridine in N-methylpyrrolidone at 20-28°C for 25-40 minutes to remove the 9-fluorenylmethoxycarbonyl protecting group on the amino group of the resin, blow dry with nitrogen, and wash with N-methylpyrrolidone; (2) Activation of amino acids: reacting the amino acids with 9-fluorenylmethoxycarbonyl protecting groups used in the synthesis with 1-hydroxybenzotriazole to synthesize amino acid-1-hydroxybenzotriazole esters; (3) Condensation reaction: Use a peptide synthesizer to automatically add the above-mentioned various amino acids, resins and diisopropylcarbodiimide to the reactor, react at 20-28°C for 0.5-2.5 hours, blow dry with nitrogen, and wash the resin with N-methylpyrrolidone; (4) Acetylation reaction: using 1.5%-4% (g / mL) acetylimidazole N-methylpyrrolidone solution by weight volume percentage to react with the resin obtained in step (3) at 20-28° C. for 20-40 minutes, drying with nitrogen, and washing the resin with methanol; (5) The synthesis process is repeated from the C-terminus to the N-terminus according to the amino acid sequence. After the reaction is completed, it is washed with N-methylpyrrolidone to obtain a dry polypeptide resin; (6) Separation of polypeptide and resin: Add a cleavage reagent (the volume ratio of each component is trifluoroacetic acid: triisopropylsilane: ethanedithiol: phenol: water = 85:8:3:3:1) to the dried polypeptide resin, stir at a constant speed for 1-4 hours, place at 0°C for reaction for 10 minutes, return to room temperature, evaporate the trifluoroacetic acid, add tert-butyl methyl ether and diethyl ether to the polypeptide solution, stir and wash, and filter to obtain a polypeptide solution; (7) Ultrafiltration purification of polypeptides and aseptic treatment: Use membrane packages to ultrafilter polypeptides at 20-28°C and use a 0.22 μm online filter for sterilization and storage.

[0035] Example 2: Preparation of polypeptide polymer A method for preparing a polypeptide polymer, comprising the following steps: (1) Take the albumin solution, filter it through a 0.45 μm filter membrane, and measure UV280 to obtain an albumin solution with a concentration of 1 mg / mL; (2) Weigh 4-(N-maleimidomethyl)cyclohexane-1-carboxylic acid 3-sulfo-N-hydroxysuccinimide ester sodium salt (Sulfo-SMCC) and dissolve it in water to obtain a Sulfo-SMCC solution with a concentration of 4 mg / mL; (3) Add 0.2 mL of Sulfo-SMCC solution to 5 mL of albumin solution and allow to react for 2 h at room temperature in the dark. Then filter through 0.2 μm for desalination to remove excess Sulfo-SMCC and obtain activated albumin. (4) mixing the amino acid sequence shown in SEQ ID NO.1, the amino acid sequence shown in SEQ ID NO.2, the amino acid sequence shown in SEQ ID NO.3, and the amino acid sequence shown in SEQ ID NO.4 at a mass ratio of 1:1:1:1 to obtain a polypeptide mixture; (5) Dissolve 6 mg of the peptide mixture in 0.6 mL of 1×PBS (pH 7.2) solution, use Ellman's reagent to detect the thiol group in the peptide, and measure its ultraviolet absorption value OD value > 0.15 at λ = 412 nm using a Nano spectrophotometer; (6) Add 0.6 mL of the polypeptide mixture solution obtained in step (5) to about 6 mg of activated albumin and let stand at room temperature in the dark for 4 h; (7) After the reaction, the thiol group in the peptide was detected by Ellman's reagent. The ultraviolet absorption value OD value measured by Nano spectrophotometer at λ = 412 nm was <0.03, indicating that the cross-linking rate between the peptide and albumin had reached more than 80%, and a peptide polymer was obtained.

[0036] Example 3: Preparation of meningococcal outer membrane protein synthetic peptide vaccine The preparation method of meningococcal outer membrane protein synthetic peptide vaccine comprises the following steps: 200 μg of the polypeptide polymer prepared in Example 2 and 1 mL of CpG solution (concentration: 200 μg / mL) were mixed to obtain a meningococcal outer membrane protein synthetic peptide vaccine.

[0037] Example 4: Immunization of mice with synthetic peptide vaccine of meningococcal outer membrane protein and detection of immunogenicity 1. Animal immunization (1) Female C57BL / 6 mice aged 6-8 weeks were selected for immunization and randomly divided into two groups, 6 mice / group, namely, CpG control group and synthetic peptide vaccine group; (2) The animals in the CpG control group were given CpG solution; the synthetic peptide vaccine group was given the meningococcal outer membrane protein synthetic peptide vaccine prepared in Example 3, with each mouse being given 10 μg of polypeptide polymer antigen and 10 μg of CpG each time, with an injection volume of 50 μL / mouse. The specific groups and numbers are shown in Table 1; (3) The immunization method was intranasal immunization. Each mouse was immunized three times, with intranasal drops on the 1st day, 7th day, and 14th day respectively; (4) One week after the last immunization, blood samples and oral lavage fluid were collected from the tail of the anesthetized mice.

[0038] Table 1 Grouping and numbering of immunized mice

[0039] 2. ELISA detects antigen-specific serum IgG. The detection steps are as follows: (1) Coating antigen: dilute meningococcal lysate to 10 μg / mL with coating solution, add 100 μL / well to a 96-well ELISA plate, and coat overnight at 4°C. (2) Blocking: Shake the coated ELISA plate dry, wash the plate five times with 300 μL of washing solution per well, pat dry, add 300 μL / well of blocking solution (2% BSA) to the plate, and place at 37°C for 2 hours; (3) Dilution of standard and test samples: dilute the standard sample (mouse IgG) to 200 ng / mL with sample diluent, and dilute it 2-fold; dilute the test sample (immune mouse serum) to 1000-10000-fold with PBS; (4) Sample loading: spin dry the blocked ELISA plate, wash the plate 5 times with 300 μL of washing solution per well, pat dry, add samples (gradient dilution standard and diluted test sample) from the dilution plate to the ELISA plate at 100 μL / well, and leave at room temperature for 1.5 h; (5) Add enzyme labeling working solution: dilute HRP-labeled goat anti-mouse IgG antibody with secondary antibody diluent; spin dry the ELISA plate, wash the plate 5 times with 300 μL of washing solution per well, pat dry, add the diluted secondary antibody to the ELISA plate at 100 μL / well, and leave at room temperature for 1 hour; (6) Color development: Wash the plate 5 times with 300 μL of washing solution per well and spin dry. Wipe the bottom with absorbent paper. Move the color development solution from the 4°C refrigerator to room temperature and keep it away from light 30 minutes in advance. Add 100 μL / well of color development solution and develop the color at room temperature and away from light for 15 minutes; (7) Termination: Add 50 μL / well of stop solution to terminate the reaction and read the plate within 5 minutes; (8) Plate reading: Place the ELISA plate into the ELISA reader, set the plate to medium speed for 10 seconds, and read the OD450.

[0040] The results are as follows Figure 1 It was shown that the serum one week after immunization with meningococcal outer membrane protein synthetic peptide vaccine contained higher levels of meningococcal-specific IgG antibodies compared with the control CpG group.

[0041] 3. ELISA detects antigen-specific secretory IgA. The detection steps are as follows: (1) Coating antigen: dilute meningococcal lysate to 10 μg / mL with coating solution, add 100 μL / well to a 96-well ELISA plate, and coat overnight at 4°C. (2) Blocking: Shake the coated ELISA plate dry, wash the plate five times with 300 μL of washing solution per well, pat dry, add 300 μL / well of blocking solution (2% BSA) to the plate, and place at 37°C for 2 hours; (3) Dilution of standard and test samples: dilute the standard sample (mouse IgA) to 200 ng / mL with sample diluent, and dilute it 2-fold; dilute the test sample (immunized mouse oral lavage fluid) to 1000-10000 times with PBS; (4) Sample loading: spin dry the blocked ELISA plate, wash the plate 5 times with 300 μL of washing solution per well, pat dry, add samples (gradient dilution standard and diluted test sample) from the dilution plate to the ELISA plate at 100 μL / well, and leave at room temperature for 1.5 h; (5) Add enzyme labeling working solution: dilute HRP-labeled goat anti-mouse IgA antibody with secondary antibody diluent; spin dry the ELISA plate, wash the plate 5 times with 300 μL of washing solution per well, pat dry, add the diluted secondary antibody to the ELISA plate at 100 μL / well, and leave at room temperature for 1 hour; (6) Color development: Wash the plate 5 times with 300 μL of washing solution per well and spin dry. Wipe the bottom with absorbent paper. Move the color development solution from the 4°C refrigerator to room temperature and keep it away from light 30 minutes in advance. Add 100 μL / well of color development solution and develop the color at room temperature and away from light for 15 minutes; (7) Termination: Add 50 μL / well of stop solution to terminate the reaction and read the plate within 5 minutes; (8) Plate reading: Place the ELISA plate into the ELISA reader, set the plate to medium speed for 10 seconds, and read the OD450.

[0042] The results are as follows Figure 2 It was shown that oral lavage fluid contained higher levels of meningococcal-specific secretory IgA antibodies one week after immunization with meningococcal outer membrane protein synthetic peptide vaccine compared with the control CpG group.

[0043] The present application discloses a synthetic peptide of meningococcal outer membrane protein and its application, and discloses a polypeptide sequence. A vaccine made from the polypeptide or its polymer can effectively deal with the diversity of meningococcal PorA and PorB antigens, is easy to synthesize on a large scale, and has good application prospects.

Claims

1. A polypeptide, characterized in that The amino acid sequence of the polypeptide is at least one of (I) to (IV): (I) the amino acid sequence shown in SEQ ID NO.1; (II) the amino acid sequence shown in SEQ ID NO.2; (III) the amino acid sequence shown in SEQ ID NO.3; (IV) The amino acid sequence shown in SEQ ID NO.

4.

2. A polypeptide polymer, characterized in that: Comprising the polypeptide of claim 1.

3. A polypeptide polymer according to claim 2, characterized in that: The polypeptide polymer also includes a carrier protein; the carrier protein includes at least one of albumin, porin, diphtheria toxin, tetanus toxin, heat-labile enterotoxin, and ferritin.

4. Use of the polypeptide according to claim 1 or the polypeptide polymer according to claim 2 or 3 in the preparation of a synthetic peptide vaccine of meningococcal outer membrane protein.

5. A synthetic peptide vaccine of meningococcal outer membrane protein, characterized in that: It comprises the polypeptide according to claim 1 or the polypeptide polymer according to claim 2 or 3.

6. A synthetic peptide vaccine of meningococcal outer membrane protein according to claim 5, characterized in that: The vaccine also includes an immune adjuvant; the immune adjuvant includes at least one of aluminum adjuvant, squalene, tocopherol, MPL, LPA, CpG and QS-21.

7. A method for preparing the polypeptide according to claim 1, characterized in that: The preparation method steps are as follows: Using the resin as a starting material, in the presence of a basic agent, an amino acid constituting the C-terminus of the peptide having an α-amino protecting group is connected to the resin; Remove the protecting group with a decapping agent; The amino acids constituting the peptide are connected in sequence from the C-terminus to the N-terminus of the peptide to react, thereby forming a peptide-connected resin, and then the peptide is cleaved and the crude product is purified to obtain a polypeptide.

8. A method for preparing the polypeptide polymer according to claim 2 or 3, characterized in that: The preparation method steps are as follows: After activating the carrier protein with 4-(N-maleimidomethyl)cyclohexane-1-carboxylic acid 3-sulfo-N-hydroxysuccinimide ester sodium salt, filtering and desalting to obtain the activated carrier protein; Mixing the polypeptide sequences of claim 1 in equal proportions to obtain a polypeptide mixture; The polypeptide mixture is coupled with the activated carrier protein to obtain a polypeptide polymer.

9. The method for preparing a polypeptide polymer according to claim 8, characterized in that: The preparation method steps are as follows: The mass ratio of the 4-(N-maleimidomethyl)cyclohexane-1-carboxylic acid 3-sulfo-N-hydroxysuccinimide ester sodium salt to the carrier protein is (0.5-1):(3-7); The volume-to-mass ratio of the polypeptide mixture to the activated carrier protein is (0.1-1) mL: (4-8) mg.

10. Use of the meningococcal outer membrane protein synthetic peptide vaccine according to claim 5 or 6, characterized in that: The application includes at least one of the following: (1) Use in the preparation of drugs for preventing and / or treating diseases caused by meningococci; (2) Use in the preparation of drugs for preventing and / or treating epidemic cerebrospinal meningitis; (3) Use in the preparation of drugs for preventing and / or treating fulminant sepsis.

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