Immunogenic oligopeptide of angiotensin II receptor type 1 and application of immunogenic oligopeptide

Abstract

The invention discloses an angiotensin II receptor type 1 immunogenic short peptide and application thereof. The amino acid sequence of the immunogenic short peptide is as shown in SEQ ID No.1: AFHYE. The effective component of the immunogenic vector vaccine is formed by coupling immunogenic oligopeptide and a vector. Immunogenic oligopeptides and a Qbeta carrier are coupled to obtain the vaccine effective component of the angiotensin II receptor type 1 immunogenic peptide fragment. The immunogenic carrier vaccine prepared from the active ingredients is used for antihypertensive treatment of primary hypertension, can be used as a long-acting antihypertensive drug, and is beneficial to improving the treatment compliance of patients with primary hypertension, so that the purpose of effectively controlling blood pressure is achieved.

Description

Technical Field

[0001] This invention relates to the fields of biopharmaceuticals and biotherapy, specifically to an immunogenic short peptide of angiotensin II receptor type 1 and its applications. Background Technology

[0002] The pathogenesis of hypertension is highly complex, involving abnormal activation of the sympathetic nervous system, the renin-angiotensin system (RAS), and the immune system. Abnormally elevated levels of vasoactive substances and immune inflammatory factors can lead to vascular remodeling and increased blood pressure, resulting in hypertension and target organ damage. The renin-angiotensin system (RAS) plays a crucial role in the development and maintenance of blood pressure. Chemotherapy drugs targeting the RAS, including renin inhibitors, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers (ARBs), have demonstrated excellent therapeutic effects in clinical practice. Despite this, global blood pressure control rates remain far from satisfactory, and treatment adherence is low. AT1 receptors, distributed in blood vessels and the heart, are G protein-coupled receptors, mainly located in the kidneys, heart, and vascular smooth muscle. When activated, they directly constrict blood vessels, raising blood pressure. Furthermore, they stimulate the sympathetic nervous system, increasing catecholamine release, reducing renal blood flow-stimulated aldosterone secretion, and controlling water intake and urinary sodium excretion—all factors contributing to elevated blood pressure.

[0003] Hypertension vaccines are a newly emerging treatment technology that has emerged in recent years. Compared with traditional chemical drugs, hypertension vaccines have potential advantages. Due to the long dosing interval and long antibody half-life, they can stably lower blood pressure and greatly improve patient compliance, making them particularly suitable for the treatment and long-term control of chronic diseases. For more than half a century, based on the important role of the RAS system in the occurrence and development of hypertension, many research teams have explored therapeutic antihypertensive vaccines that target the RAS. The initial renin whole antigen vaccine had a significant antihypertensive effect, but the adverse outcome of causing kidney damage limited the development of the vaccine [Brown MJ. Success and failure of vaccines against renin-angiotensin system components. Nat Rev Cardiol, 2009, 6: 639–647; Qiu Z, Chen X, Zhou Y, et al. Therapeutic vaccines against human and rat renin in spontaneously hypertensive rats. PLoS ONE, 2013, 8: e66420]. In our previous research, a therapeutic vaccine targeting angiotensin II type 1 receptor (AT1R) demonstrated promising efficacy [Zhu F, Liao Y, Li L, et al. Target organ protection from a novel angiotensin II receptor (AT1) vaccine ATR12181 in spontaneously hypertensive rats. Cell Mol Immunol, 2006, 3: 107–114]. Furthermore, based on our experience and repeated experiments, our research team identified and demonstrated that an epitope of human AT1R can reduce systolic blood pressure (SBP) in spontaneously hypertensive rats (SHR) and provide good protection in target organs [Chen X, Qiu Z, Yang S, et al. Effectiveness and safety of a therapeutic vaccine against angiotensin II receptor type 1 in hypertensive animals. Hypertension, 2013, 61: 408–416].Meanwhile, international teams have also confirmed that short peptide vaccination against AT1R can not only effectively lower blood pressure but also prevent L-NAME-induced nephropathy [Azegami T, Sasamura H, Hayashi K, et al. Vaccination against theangiotensin type 1 receptor for the prevention of L-NAME-induced nephropathy. Hypertens Res, 2012, 35: 492–499]. We are currently conducting related translational research with the aim of applying it clinically.

[0004] One of the purposes of designing short AT1R peptide epitopes instead of long sequences is to reduce potential autoimmune damage. Generally, the shorter the antigen peptide, the less likely it is to cause autoimmune damage. In order to minimize the potential autoimmune damage while ensuring effectiveness, we further shortened the previously invented AT1R short peptide to compare its effectiveness.

[0005] However, short peptides alone are difficult to induce an effective immune response. In order to improve the low immunogenicity of AT1R, it is combined with a virus-like particle (VLP) carrier protein (VLP is characterized by a highly repetitive and ordered surface structure, which can load a large number of epitopes on the carrier surface, has a strong antigen presentation ability, and induces a strong immune response). This strategy has been used in the development of drugs for various chronic diseases. Summary of the Invention

[0006] The purpose of this invention is to overcome the shortcomings of the prior art and provide an immunogenic short peptide of angiotensin II receptor type 1 and its application. This invention can utilize this immunogenic short peptide to produce a vaccine of AT1 receptor immunogenic peptide, which can be used for antihypertensive treatment of essential hypertension. It can be used as a long-acting antihypertensive drug, which helps to improve the treatment compliance of patients with essential hypertension, thereby achieving the goal of effectively controlling blood pressure.

[0007] To achieve the above objectives, the technical solution designed by the present invention is as follows: This invention provides an immunogenic short peptide of angiotensin II receptor type 1, the amino acid sequence of which is shown in SEQ ID No. 1: AFHYE.

[0008] The present invention also provides an effective component of an immunogenic vector vaccine for angiotensin II receptor type 1, wherein the effective component of the immunogenic vector vaccine is formed by coupling the above-mentioned immunogenic short peptide with a carrier.

[0009] Furthermore, the immunogenic short peptide has a linker short peptide CGG added to its C-terminus for coupling with the vector (three amino acids CGG are added to the C-terminus of the short peptide during synthesis to facilitate coupling with the vector); the amino acid sequence of the short peptide CQ8 formed by adding the linker short peptide is shown in SEQ ID No. 2: CGGAFHYE; The carrier is an activated Qβ carrier.

[0010] This invention also provides a method for preparing the effective component of the above-mentioned angiotensin II receptor type 1 immunogenic vector vaccine, comprising the following steps: 1) When synthesizing the immunogenic short peptide, add three amino acids CGG to the C-terminus of the short peptide to form the short peptide CQ8, whose amino acid sequence is shown in SEQ ID No.2: CGGAFHYE; 2) Dissolve the short peptide CQ8 in filtered PBS, mix the activated Qβ carrier with the short peptide CQ8 at a mass ratio of 1:1, shake, and obtain a conjugate containing free substances. 3) Place the above conjugate in a dialysis bag, dialyze, and collect the conjugate after dialysis, which is the effective component of the immunogenic vector vaccine.

[0011] Further, in step 1), the Qβ carrier is prepared by the following steps: a. Dissolve the coupling agent SMCC in DMSO to obtain an SMCC solution. Adjust the SMCC concentration with PBS, then add the Qβ carrier to the SMCC solution, mix well, and incubate in a 37°C water bath. b. Add the solution after the reaction to a 100kD ultrafiltration tube and centrifuge; the activated Qβ carrier is obtained.

[0012] The present invention also provides the application of the active ingredient of an angiotensin II receptor type 1 immunogenic vector vaccine in the preparation of an antihypertensive drug for essential hypertension.

[0013] The present invention also provides an immunogenic vector vaccine antihypertensive drug for primary hypertension, wherein the antihypertensive drug comprises the above-mentioned immunogenic vector vaccine active ingredient and pharmaceutically acceptable excipients.

[0014] Furthermore, the excipient is an adjuvant containing aluminum hydroxide.

[0015] This invention also provides a method for preparing the above-mentioned immunogenic vector vaccine antihypertensive drug, comprising the following steps: 1) Dilute aluminum hydroxide solution (Al(OH)3) and the effective component of immunogenic vector vaccine with PBS, and adjust the pH to 6.3 for both. 2) Add the diluted aluminum hydroxide solution to the diluted effective component of the immunogenic vector vaccine, mix them evenly in equal volumes to obtain the immunogenic vector vaccine.

[0016] Furthermore, the antihypertensive drug contains 0.1 mg / mL of aluminum, 1 mg / mL of the effective component of the immunogenic vector vaccine, and 0.01 mol / L of PBS buffer salt.

[0017] The beneficial effects of this invention are: This invention provides an immunogenic short peptide of angiotensin II receptor type 1 (AT1 receptor). The immunogenic short peptide is coupled with a Qβ carrier to obtain the active vaccine component of the immunogenic peptide segment of angiotensin II receptor type 1 (AT1 receptor). This active component can be used to prepare an immunogenic vector vaccine for the antihypertensive treatment of essential hypertension. It can serve as a long-acting antihypertensive drug, helping to improve treatment adherence in patients with essential hypertension, thereby achieving effective blood pressure control. Attached Figure Description

[0018] Figure 1 This is an image showing the SDS-PAGE electrophoresis results of the conjugated sample (immunogenic vector vaccine active ingredient) obtained in Example 1; In the figure, the order of spotting is: M: Marker; 1, 3 and 6: Qβ vector (load amount: 1.5 μg); 2, 4 and 5: conjugate (i.e., the effective component of the immunogenic vector vaccine, load amount: 15 μg). Figure 2 This is a schematic diagram showing the changes in blood pressure of SHR rats in each group at each experimental stage in Example 3; In the picture, black Indicates that the vaccine experimental immunization group and positive control group are compared with the adjuvant negative control group (P<0.05); blue indicates that the difference is significant. Or black The result indicates that the vaccine control immunization group or all immunization groups were compared with the adjuvant negative control group (P<0.01).

[0019] Figure 3 This is a schematic diagram showing the blood pressure reduction amplitude of each group of SHR rats in each experimental stage in Example 3; In the figure, ns represents the inter-group comparison P>0.05. This indicates a p-value < 0.05 between groups. This indicates a p-value < 0.01 between groups.

[0020] Figure 4 This is a schematic diagram of antibody titers in the serum of SHR rats in each immunization group in Example 3.

[0021] In the figure, ns represents the inter-group comparison P>0.05. This indicates a p-value < 0.05 between groups. This indicates a p-value < 0.01 between groups. Detailed Implementation

[0022] The present invention will now be described in further detail with reference to specific embodiments, so that those skilled in the art can understand it.

[0023] Example 1: Preparation of the active ingredient of an angiotensin II receptor type 1 immunogenic vector vaccine I. Synthesis of immunogenic short peptides of angiotensin II receptor type 1 (AT1 receptor immunogenic peptides) An immunogenic short peptide (truncated ATR001) with the same antigenicity as the extracellular second cyclic peptide fragment of angiotensin II receptor type 1 (AT1 receptor) was synthesized, namely as shown in SEQ ID No. 1: AFHYE. At the same time, a linker short peptide (three amino acid sequence CGG) was added to the C-terminus of the peptide to form the short peptide CQ8, whose amino acid sequence is shown in SEQ ID No. 2: CGGAFHYE.

[0024] II. Preparation of the effective components of angiotensin II receptor type 1 immunogenic vector vaccine: 1) Activation: After the concentration of Qβ carrier was detected by BCA method, 3 mg of coupling agent SMCC was dissolved in 5.4 mg DMSO (adjusted to 100 mg / mL) to obtain SMCC solution. The concentration of SMCC was adjusted to 20 mg / mL with filtered PBS. Qβ carrier and SMCC were mixed and placed in a 37℃ water bath for 30 min. The mixture was gently shaken once every 10 min. 2) Removal of free SMCC: After the reaction, add the solution to a 100kD ultrafiltration tube and centrifuge at 5000g at 4℃ for 10min; this is the activated Qβ carrier. 3) Conjugation: Dissolve 3 mg of short peptide in filtered PBS (adjust the concentration to 10 mg / mL), mix the activated Qβ carrier with the short peptide at a ratio of 1 mg: 1 mg, and shake at 300 rpm for 2 h at room temperature, gently shaking once every 30 min to obtain a conjugate containing free substances (excess short peptide and Qβ carrier); 4) Removal of free peptides: The conjugate containing free substances is placed in a 14kDa dialysis bag and dialyzed with 0.01mol / L PBS at 2-8℃ for 24h. The conjugate after dialysis is collected, which is the effective component of the immunogenic vector vaccine.

[0025] III. SDS-PAGE electrophoresis detection of the conjugation effect of the above-mentioned immunogenic vector vaccine active ingredients The concentrations of the conjugate (immunogenic vector vaccine active ingredient) and the control (Qβ vector) were determined using the BCA method. 15 μL and 1.5 μL of protein loading buffer were added to each, and the mixture was boiled at 100°C for 15 minutes. The mixture was then added to an SDS-PAGE gel containing a 15% separating gel and a 5% stacking gel. The voltage was adjusted to 90 V. When the bands reached the lower separating gel layer, the voltage was adjusted to 120 V, and the electrophoresis was stopped when the bands were about to exit the gel. After carefully peeling the gel, Coomassie Brilliant Blue rapid staining solution was added for 1 hour, followed by destaining with ddH2O until clear. The gel was then photographed using a gel imaging system and saved.

[0026] like Figure 1 As shown in Table 1, the Qβ vector coupled with the short peptide CQ8 (CGGAFHYE) does not contain monomers, and it is more common to couple with 2-3 short peptides. The average coupling rate is 2.62, that is, each Qβ vector molecule couples with an average of 2.62 short peptides.

[0027] Table 1. Percentage of SDS-PAGE bands

[0028] Note: The weighted average represents the average number of short peptides conjugated to each Qβ vector.

[0029] Example 2: Preparation of an immunogenic vector vaccine for essential hypertension The method for preparing an immunogenic vector vaccine antihypertensive drug for essential hypertension includes the following steps: 1) Dilute the aluminum hydroxide solution (Al(OH)3) and the immunogenic vector vaccine active ingredient liquid with PBS, and adjust the pH to 6.3 for both. 2) Add the diluted aluminum hydroxide solution to the diluted liquid of the effective component of the immunogenic vector vaccine, mix evenly with equal volume, shake thoroughly, and adsorb at 2-8℃ for 24 hours (intermittent shaking) to obtain the immunogenic vector vaccine antihypertensive drug; wherein, in the immunogenic vector vaccine antihypertensive drug, the aluminum content is 0.1 mg / mL, the effective component content is 1 mg / mL, and the PBS buffer salt concentration is 0.01 mol / L.

[0030] Comparative Example 1 The components of the comparative vaccine and the immunogenic vector vaccine prepared in Example 2 are basically the same, the difference being: The short peptide sequence CQ10 is CGGAFHYESQ, as shown in SEQ ID No. 4, which contains the short peptide ATR001, as shown in SEQ ID No. 3: AFHYESQ.

[0031] Example 3: The antihypertensive effect of the above-mentioned immunogenic vector vaccine (a vaccine containing the AT1 receptor immunogenic peptide) on spontaneously hypertensive (SHR) rats. Six-week-old male SHR rats were immunized with the immunogenic vector vaccine (containing the short peptide sequence AFHYE) prepared in Example 2 and the control vaccine (containing the short peptide sequence AFHYESQ) prepared in Comparative Example 1. The immune effects and antihypertensive effects of the two vaccines were evaluated by observing body weight, detecting blood pressure, and detecting serum antibodies by ELISA.

[0032] I. Animal grouping and administration 1. Animal grouping: All animals were randomly divided into the following groups: a. Adjuvant negative control group, b. Positive control group c. Vaccine experimental immunization group, d. Vaccine control group.

[0033] 2. Administration: Adjuvant negative control group: subcutaneous injection of aluminum hydroxide solution, Positive control group: Valsartan aqueous solution administered by gavage. Vaccine experimental immunization group: subcutaneous injection of immunogenic vector vaccine, Vaccine control group: Subcutaneous injection of control vaccine; i. Select the following time points for subcutaneous injection: D1, D15, D29 (that is, Day 1, Day 15, and Day 29 at the start of the experiment, hereinafter referred to as the same), for a total of 3 times (each time after blood pressure measurement and blood collection). Dosage: 250 μg / animal / dose.

[0034] ii. The positive control group was administered the medication by gavage. The administration time was from D15 to D70, once a day (no medication was given before the blood pressure measurement on the day of the measurement, and the medication was given after the measurement). Dosage: Valsartan aqueous solution 3 mg / kg / day.

[0035] II. General clinical observation and weight monitoring 1. General clinical observation: During all animal experiments, observe at least twice a day (once in the morning and once in the afternoon) and record any observed animal deaths and abnormal clinical manifestations.

[0036] 2. Weight monitoring: Weight was measured and recorded at D0, D14, D28, D42, D56, and D70 during all animal experiments.

[0037] III. Blood Pressure Measurement 1. Blood Pressure and Heart Rate Measurement Method: Turn on the intelligent non-invasive blood pressure monitor, place the rat in a rat net and then in an insulated container, with its tail inside the infrared detector. Adjust the insulated container to an appropriate temperature range (36~39℃), and wrap the container with a rat bag. After the animal has calmed down, measure the blood pressure and heart rate at the base of the rat's tail. Measure the blood pressure and heart rate of each animal 8 times at each time point, and then calculate the average. If any systolic blood pressure reading differs from the average by more than 10 mmHg from any of the 8 readings, discard that result and repeat the measurement.

[0038] 2. Testing time points: D0 (before the first immunization), D14 (before the second immunization), D28 (before the third immunization), D42, D56, and D70, each tested once. The positive control group was administered the drug 24 hours in advance and administered the drug after testing on the same day.

[0039] IV. Blood collection and indirect ELISA detection of antibody titers 1. Blood collection: Wipe the rat's tail with an alcohol swab, dry it, cut off the tail and collect the blood. After the blood has been left to stand at 37°C for 30 minutes, centrifuge at 2500g at room temperature for 20 minutes and aspirate the serum.

[0040] 2. Testing time points: D14 (before the second immunization), D28 (before the third immunization), D42, D56, and D70, after measuring blood pressure.

[0041] 3. Indirect ELISA detection steps: ① Coating: After conjugating the short peptide CQ8 with BSA (vector), dilute it to a concentration of 1.5 µg / well with coating buffer; dilute the Qβ vector to a concentration of 0.1 µg / well, add 100 µL to each well and incubate overnight at 4°C.

[0042] ② Washing: Use 300µL of PBST per well and wash 3 times with a plate washer.

[0043] ③ Sealing: Add 150µL of 2% BSA to each well and seal overnight at 37℃.

[0044] ④ Primary antibody: Add 100µL of diluted positive and negative sera to each well. The primary antibody dilutions are 1:1000, 1:2500, 1:5000, 1:20000, 1:40000, 1:80000, 1:160000, 1:320000, and 1:640000. Incubate at 37℃ for 1 hour.

[0045] ⑤ Washing: Wash 5 times with 300µL of PBST per well.

[0046] ⑥ Secondary antibody: Add 100µL of HRP-goat anti-rat IgG (H+L) diluted 1:3000 to each well and incubate at 37℃ for 45 min.

[0047] ⑦ Washing: Wash 5 times with 300µL of PBST per well.

[0048] ⑧ Color development: Add 100µL of substrate color development solution to each well in the dark, and incubate at 37℃ in the dark for 8 minutes.

[0049] ⑨ Termination of reaction: Add 100µL of reaction termination solution to each well in the dark, and measure OD. 450nm value.

[0050] V. Results Analysis 1. Changes in body weight of SHR rats in each group at each experimental stage As can be seen from the data in Table 2, the weight of SHR rats in each group gradually increased throughout the experimental period, and the average weight of SHR rats in each group was uniform across all stages (P>0.05).

[0051] Table 2. Weight monitoring results of SHR rats in each group at each experimental stage.

[0052] Note: Values ​​are expressed as mean ± standard deviation, in kg.

[0053] 2. Blood pressure changes in SHR rats in each group at each experimental stage As shown in Table 3, compared with the adjuvant negative control group, there was no significant difference in the mean blood pressure (SBP) of all SHR rats before immunization and 2 weeks after the first immunization (P>0.05). After the second immunization, each immunization group (vaccine experimental immunization group and vaccine control immunization group) and the positive control group showed a certain antihypertensive effect compared with the adjuvant negative control group (8 mmHg, P>0.05). After the third immunization, there was no significant difference in the antihypertensive effect among each immunization group and the positive control group (P>0.05), but compared with the adjuvant negative control group, each immunization group showed a significant antihypertensive effect (P<0.01), with a reduction of 7-9 mmHg at the end of the 6th week, 11-12 mmHg at the end of the 8th week, and 16-17 mmHg at the end of the 10th week.

[0054] Table 3. Blood pressure measurement results of SHR rats in each group at each experimental stage.

[0055] Note: Values ​​are expressed as mean ± standard deviation, in mmHg.

[0056] 3. Serum antibody titers of SHR rats in each group As shown in Table 4 and Figure 4It was found that the titer of the immunogenic short peptide in the serum of SHR rats in the vaccine control group was significantly higher than that in the vaccine experimental group at each stage of the experimental cycle (P<0.01). In week 2 (2 weeks after the first immunization), the titer of the Qβ carrier in the serum of SHR rats in the vaccine control group was not significantly different from that in the vaccine experimental group (P>0.05). In week 4 (2 weeks after the second immunization), the titer of the Qβ carrier in the serum of SHR rats in the vaccine control group was higher than that in the vaccine experimental group (P<0.05). In weeks 6, 8, and 10 (after the third immunization), the titer of the Qβ carrier in the serum of SHR rats in the vaccine control group was higher than that in the vaccine experimental group (P<0.01).

[0057] Table 4. Serum antibody titer detection results of SHR rats in each group at each experimental stage.

[0058] 4. Conclusions and Analysis The average body weight of SHR rats was uniform across all groups throughout the entire experimental period.

[0059] Throughout the experimental period, compared with the adjuvant-negative control group, the mean blood pressure of the vaccine-immunized group and the vaccine-controlled group showed consistent antihypertensive effects (P>0.05); the second immunization showed a certain antihypertensive effect (8 mmHg, P>0.05), and the third immunization showed a significant antihypertensive effect (P<0.01), with a reduction of 7-9 mmHg at the end of week 6, 11-12 mmHg at the end of week 8, and 16-17 mmHg at the end of week 10.

[0060] The study suggests that immunization of SHR rats with immunogenic short peptide (AFHYE) can still effectively reduce blood pressure, indicating that the five amino acid segments of the immunogenic short peptide are the core sites of AT1R receptor function.

[0061] At each stage of the experimental cycle, the titer of the immunogenic short peptide in the serum of SHR rats in the vaccine control group was significantly higher than that in the vaccine experimental group (P<0.01). In week 2 (2 weeks after the first immunization), the titer of the Qβ carrier in the serum of SHR rats in the vaccine control group was not significantly different from that in the vaccine experimental group (P>0.05). In week 4 (2 weeks after the second immunization), the titer of the Qβ carrier in the serum of SHR rats in the vaccine control group was higher than that in the vaccine experimental group (P<0.05). In weeks 6, 8, and 10 (after the third immunization), the titer of the Qβ carrier in the serum of SHR rats in the vaccine control group was higher than that in the vaccine experimental group.

[0062] In summary, the immunogenic vector vaccine produced lower antibody titers in SHR rats compared to the control vaccine, and truncating the ATR001 peptide weakened its immunogenicity. However, the CQ8 short peptide vaccine had comparable antihypertensive effects to the 7-peptide vaccine, indicating that the five peptides in this vaccine are key peptides of AT1R, and the antibodies produced can effectively lower blood pressure. Furthermore, the short peptide of this invention, due to its shorter sequence, has better safety and can be better applied in clinical practice in the future.

[0063] All other parts not described in detail are existing technologies. Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, not all embodiments. People can obtain other embodiments based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. An immunogenic short peptide of angiotensin II receptor type 1, characterized in that: The amino acid sequence of the immunogenic short peptide is shown in SEQ ID No.

1.

2. An immunogenic vector vaccine for angiotensin II receptor type 1, characterized in that: The effective component of the immunogenic vector vaccine is formed by coupling the immunogenic short peptide described in claim 1 with a carrier.

3. The active ingredient according to claim 2, characterized in that: The immunogenic short peptide has a linker short peptide CGG added to its C-terminus for coupling with the vector. The amino acid sequence of the short peptide CQ8 formed by adding the linker short peptide is shown in SEQ ID No.

2. The carrier is an activated Qβ carrier.

4. A method for preparing the effective component of an angiotensin II receptor type 1 immunogenic vector vaccine as described in claim 3, comprising the following steps: 1) When synthesizing the immunogenic short peptide, add three amino acids CGG to the C-terminus of the short peptide to form the short peptide CQ8, whose amino acid sequence is shown in SEQ ID No. 2; 2) Dissolve the short peptide CQ8 in filtered PBS, mix the activated Qβ carrier with the short peptide CQ8 at a mass ratio of 1:1, shake, and obtain a conjugate containing free substances. 3) Place the above conjugate in a dialysis bag, dialyze, and collect the conjugate after dialysis, which is the effective component of the immunogenic vector vaccine.

5. The preparation method according to claim 4, characterized in that: In step 2), the activated Qβ carrier is prepared by the following steps: a. Dissolve the coupling agent SMCC in DMSO to obtain an SMCC solution. Adjust the SMCC concentration with PBS, then add the Qβ carrier to the SMCC solution, mix well, and incubate in a 37°C water bath. b. Add the solution after the reaction is complete into an ultrafiltration tube and centrifuge; the activated Qβ carrier is obtained.

6. The application of an effective component of an angiotensin II receptor type 1 immunogenic vector vaccine in the preparation of an antihypertensive drug for essential hypertension.

7. An immunogenic vector vaccine-based antihypertensive drug for essential hypertension, characterized in that: The antihypertensive drug comprises the active ingredient of the immunogenic vector vaccine as described in claim 2 or 3 and pharmaceutically acceptable excipients.

8. The immunogenic vector vaccine antihypertensive drug according to claim 7, characterized in that: The excipient is an adjuvant containing aluminum hydroxide.

9. A method for preparing an immunogenic vector vaccine antihypertensive drug according to claim 8, characterized in that: Includes the following steps: 1) Dilute the aluminum hydroxide solution and the effective component of the immunogenic vector vaccine separately with PBS, and adjust the pH of both. 2) Add the diluted aluminum hydroxide solution to the diluted effective component of the immunogenic vector vaccine, mix them evenly in equal volumes to obtain the immunogenic vector vaccine.

10. The method for preparing the immunogenic vector vaccine antihypertensive drug according to claim 9, characterized in that: The antihypertensive drug contains 0.1 mg / mL of aluminum, 1 mg / mL of the effective component of the immunogenic vector vaccine, and 0.01 mol / L of PBS buffer salt.

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