Peptide vaccine compositions and pharmaceutical preparations for reducing the progression of atherosclerosis

Abstract

A peptide vaccine composition for reducing the progression of atherosclerosis comprises peptides derived from the E3 region of the TRPM2 ion channel from various species, either alone or in combination. A pharmaceutical formulation comprises the peptide vaccine composition and an adjuvant. By utilizing the TRPM2 peptides, the peptide vaccine composition and pharmaceutical formulation of the present invention are capable of producing effective anti-TRPM2 polyclonal antibodies that can reduce the progression of atherosclerosis in an apoE knockout mouse model. Furthermore, the present invention identifies the most suitable antigen delivery pathway for endogenously producing anti-TRPM2 polyclonal antibodies to alleviate atherosclerosis.

Description

Technical Field

[0001] The present invention relates to peptide vaccine compositions and pharmaceutical preparations for reducing atherosclerosis. Background Art

[0002] Atherosclerosis is the main cause of coronary heart disease, cerebral infarction, and peripheral vascular disease. Lipid metabolism disorders are the pathological basis of atherosclerosis. Its characteristic is that the lesions of the affected arteries start from the intima, generally first with the accumulation of lipids and complex carbohydrates, bleeding and thrombosis, followed by fibrosis and calcification, and the gradual degeneration and calcification of the middle layer of the artery, leading to thickening and hardening of the arterial wall and narrowing of the blood vessel lumen. The lesions often involve large and medium muscular arteries. Once they develop enough to block the arterial lumen, the tissues or organs supplied by the artery will be ischemic or necrotic. Because the lipids accumulated in the intima of the artery appear yellow and porridge-like, it is called atherosclerosis. How to obtain drugs that can effectively reduce the progression of atherosclerosis is a problem faced by the existing technology.

[0003] It should be noted that the information disclosed in the above background technology section is only used to understand the background of this application, and therefore may include information that does not constitute prior art known to ordinary technicians in this field. Summary of the Invention

[0004] The main purpose of the present invention is to overcome the defects of the above-mentioned background technology and provide a TRPM2-based peptide vaccine composition and pharmaceutical preparation to reduce the progression of atherosclerosis.

[0005] To achieve the above object, the present invention adopts the following technical solutions:

[0006] A peptide vaccine composition for reducing the progression of atherosclerosis comprises peptides derived from the E3 region of the TRPM2 ion channel of various species, alone or in combination.

[0007] Furthermore, the peptide vaccine composition comprises a combination of one or more of the peptide P1 (HNERRVEWIFRGAVYQ) based on pig sequence, the peptide R1 (PHDGRLEWIFRRVLYR) based on rabbit sequence, the peptide R2 (FGQIPLDEIDEARVNCSVH) based on rabbit sequence, and the peptide H2 (FGQIPGYIDGVNFNPEHCSPN) based on human sequence.

[0008] Furthermore, the peptide vaccine composition contains at least peptide P1 (HNERRVEWIFRGAVYQ).

[0009] Furthermore, the peptide vaccine composition contains at least peptide R1 (PHDGRLEWIFRRVLYR).

[0010] Furthermore, the combination comprises peptides R1+R2.

[0011] A pharmaceutical preparation comprises the peptide vaccine composition and an adjuvant.

[0012] Furthermore, the pharmaceutical preparation is a pharmaceutical preparation administered by subcutaneous injection and is used as a vaccine for treating atherosclerosis.

[0013] The peptide vaccine composition targets the E3 region of the TRPM2 ion channel.

[0014] Furthermore, the adjuvant includes Freund's adjuvant and / or aluminum salt.

[0015] In a preferred embodiment, the pharmaceutical preparation consists of a dose of 2.5 mg / kg body weight of the TRPM2 peptide vaccine P1 (HNERRVEWIFRGAVYQ) and an aluminum salt as an adjuvant.

[0016] The invention relates to a use of the peptide vaccine composition for preparing a drug for treating and preventing atherosclerosis and heart diseases associated with atherosclerosis.

[0017] In some embodiments, the peptide vaccine formulation is composed of a peptide derived from the E3 region of the TRPM2 ion channel and a suitable adjuvant, at an optimized dose for the treatment and prevention of atherosclerosis and heart diseases associated with atherosclerosis.

[0018] In some embodiments, peptide vaccines stimulate the formation of peptide-specific T cells and antibody responses. By inference, T cells and antibodies specific to the E3 region of the TRPM2 ion channel will have similar effects. Treatment using lymphoid cells and / or antibodies specific to the E3 region of the TRPM2 ion channel is also an equivalent alternative to TRPM2 vaccine peptide preparations.

[0019] The inventors have tested the vaccine formulation in an ApoE knockout mouse model that developed atherosclerosis after being fed a high cholesterol diet for three months. "Slowed" or "reduced" or "inhibited" means that after injection, the formulation consisting of the porcine TRPM2 peptide vaccine reduced the total atherosclerotic lesion area in the ApoE knockout mouse model by 14% (compared to the KLH control).

[0020] The use of vaccine formulations is relevant for novel vaccine therapies and preventive treatments of atherosclerotic diseases which are currently underway in mammals and are further supported by clinical trials in humans.

[0021] The inventors tested and demonstrated that the use of the vaccine formulation was effective in slowing down / inhibiting the development / progression of atherosclerosis in an ApoE knockout mouse model.

[0022] The vaccine composition may be used as a monotherapy or in combination with other anti-atherosclerotic treatments.

[0023] As an example, the use of the vaccine formulation was tested in an ApoE mouse model injected with two different doses of the vaccine: 135 μg per mouse (5 mg / kg body weight) and 67.5 μg per mouse (2.5 mg / kg body weight). These doses were used for ApoE knockout mice based on the severity of atherosclerosis after feeding a high cholesterol diet, the age, weight, general health of the animal, sex, time of administration, route of administration, and other similar factors well known in the medical field. When used in other species, including humans, the dose needs to be adjusted based on the above factors.

[0024] Compared with the prior art, the present invention has the following beneficial effects:

[0025] The peptide vaccine compositions and pharmaceutical formulations of the present invention utilize the aforementioned TRPM2 peptides to generate effective anti-TRPM2 polyclonal antibodies that can reduce the progression of atherosclerosis in an ApoE knockout mouse model. Furthermore, the present invention identifies the most suitable antigen delivery pathway for endogenously producing anti-TRPM2 polyclonal antibodies to alleviate atherosclerosis. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 Shows a schematic experimental progress.

[0027] Figure 2 Lipid profile analysis showing serum cholesterol and serum LDL levels in response to a high cholesterol diet and a normal diet.

[0028] Figure 3 Elisa analysis showing that the present invention examples produce antigen-specific antibodies in animals immunized with P1, R1, and H2.

[0029] Figure 4 It was shown that the porcine peptide P1 and the rabbit peptide R1 as well as the combination of R1+R2 according to the examples of the present invention reduced the progression of atherosclerosis.

[0030] Figure 5 The present invention demonstrates that in tissue section staining, P1 treatment reduces the area of ​​atherosclerotic lesions in necrotic core analysis.

[0031] Figure 6 The results showed that the treatment with Example P1 of the present invention reduced the atherosclerotic lesion area in Oil Red O staining.

[0032] Figure 7 Lipid profile analysis showing the effect of immunization with the peptides of the present invention on serum cholesterol and serum LDL levels.

[0033] Figure 8 This shows that Examples P1 and R1 of the present invention can reduce the progression of atherosclerosis when used with various adjuvants.

[0034] Figure 9 The difference between the two adjuvants used in the examples of the present invention and Freund's adjuvant is shown.

[0035] Figure 10 The examples of the present invention show that the anti-atherosclerotic effects of peptide antigen P1 are compared with those of simvastatin.

[0036] Figure 11 It was shown that Example P1 of the present invention can reduce the size of the necrotic core when aluminum salt or Freund's adjuvant or Freund's adjuvant is used.

[0037] Figure 12 It was shown that Example R1 of the present invention can reduce the size of the necrotic core when Freund's adjuvant is used.

[0038] Figure 13 This shows that Example P1 of the present invention also has a better effect than simvastatin in reducing the size of the necrotic core.

[0039] Figure 14 It was shown that Example P1 of the present invention also reduced the Oil Red O-positive area in Oil Red O staining of aortic root tissue.

[0040] Figure 15 It was shown that Example P1 of the present invention reduced MPO staining in the immunostaining of MPO and CD68, but had no significant effect on CD68 staining. DETAILED DESCRIPTION

[0041] The following is a detailed description of the embodiments of the present invention. It should be emphasized that the following description is only exemplary and is not intended to limit the scope of the present invention and its application.

[0042] Peptide antigen design, experimental protocol, lipid profile, and antibody generation

[0043] We designed five different peptide antigen combinations targeting the E3 region of the TRPM2 channel, including: peptide P1 (HNERRVEWIFRGAVYQ) based on a porcine sequence, peptide R1 (PHDGRLEWIFRRVLYR) based on a rabbit sequence, peptide R2 (FGQIPLDEIDEARVNCSVH) based on a rabbit sequence, peptide R1+R2, and peptide H2 (FGQIPGYIDGVNFNPEHCSPN) based on a human sequence. These peptides were subcutaneously immunized into ApoE knockout mice, followed by two booster doses on days 21 and 42, respectively. The animals were fed a high-cholesterol diet for an additional three months to promote the development of atherosclerosis, or a normal diet as a control group. The animals were then sacrificed and samples were subsequently analyzed. A schematic experimental schedule is shown below. Figure 1 Lipid profile analysis confirmed that a high cholesterol diet did increase serum cholesterol and serum LDL levels ( Figure 2 Elisa analysis confirmed the production of antigen-specific antibodies in animals immunized with P1, R1, and H2 ( Figure 3 It should be noted that the antibody production from H2 peptide immunization is too high and may be harmful to health, which may explain why several animals immunized with H2 died.

[0044] See also Figure 2 As expected, ApoE knockout mice fed a high-cholesterol diet had elevated serum cholesterol and LDL levels. However, the high-cholesterol diet had little effect on serum triglyceride levels.

[0045] See also Figure 3 As can be seen, P1 and R1 induce moderate antibody production, detectable three months after immunization. H2 induces substantial antibody production, which may be harmful. Some animals immunized with H2 died, likely due to an excessive immune response to the H2 peptide. R2 does not induce significant antibody production.

[0046] Immunization with peptide antigens in the form of vaccines inhibits atherosclerosis progression in ApoE knockout mice

[0047] The aortas of the animals were dissected and the effects of peptide antigens on atherosclerotic plaques were examined by Oil Red O staining of the aorta whole-mounts, Oil Red O staining of tissue sections of the aortic root, and analysis of the fibrotic and necrotic cores of tissue sections of the aortic root. The results of Oil Red O staining of the aorta whole-mounts showed that the pig-derived peptide P1 and the rabbit-derived peptide R1 and the combination of R1+R2 (all from rabbits) significantly reduced the progression of atherosclerosis ( Figure 4 ), among which P1 has the best effect ( Figure 4Next, we selected P1 for further analysis. In the tissue section staining, P1 treatment showed a significant difference in necrotic core analysis ( Figure 5 ) and Oil Red O staining ( Figure 6 ) reduced the area of ​​atherosclerotic lesions.

[0048] See also Figure 4 As expected, all animals fed a high-cholesterol diet developed atherosclerosis, while animals fed a normal diet did not. Immunization with P1, R1, and R1+R2 significantly reduced atherosclerosis progression compared to a control group that did not receive peptide immunization. Of the three treatments, P1 was the most effective, reducing the area of ​​atherosclerotic lesions from 38% to 28%, a 10% reduction.

[0049] See also Figure 5 As expected, animals fed a high cholesterol diet developed fibrosis, while animals fed a normal diet had little / no fibrosis. Immunization with P1 reduced the area of ​​fibrosis (blue) compared to the control group that was not immunized with peptide. More significantly, P1 reduced the size of the necrotic core. Figure 3 The results of , which showed a higher effectiveness of P1 immunization, were presented, with only P1 being investigated in the tissue section analysis.

[0050] See also Figure 6 As expected, animals fed a high-cholesterol diet developed atherosclerosis, whereas animals fed a normal diet did not. Importantly, immunization with P1 reduced the progression of atherosclerosis as measured by Oil Red O staining compared to a control group that was not immunized with the peptide. Figure 4 The results of , which showed the highest effectiveness of P1 immunization, were only investigated in the tissue section analysis.

[0051] In summary, we discovered two potent TRPM2 peptide antigens, termed P1 and R1, that can reduce atherosclerosis progression in apoE knockout mice fed a high-cholesterol diet, with P1 being more effective.

[0052] result

[0053] Based on the results of Part 1, we selected P1 and R1 for further studies using subcutaneous injections. The goal of this step was to find the optimal doses of peptides P1 and R1, as well as the best adjuvant. Two different doses of P1 and R1 were used: 135 μg per mouse (5 mg / kg body weight) and 67.5 μg per mouse (2.5 mg / kg body weight). We also tested two commonly used adjuvants, Freund's adjuvant and aluminum salts. Freund's adjuvant is the most commonly used adjuvant in animal immunization, while aluminum salts are the most commonly used adjuvant in human vaccines.

[0054] Lipid profile

[0055] ApoE knockout mice were subcutaneously immunized with KLH-coupled peptides P1 (HNERRVEWIFRGAVYQ) and R1 (PHDGRLEWIFRRVLYR), followed by two booster doses on days 21 and 42, respectively. The peptide-to-KLH ratio was 1:1. The animals were fed a high-cholesterol diet for an additional three months to promote the development of atherosclerosis. The animals were then sacrificed, and samples were subsequently analyzed.

[0056] Two different doses of P1 and R1 were used, 135 μg per mouse (5 mg / kg body weight) and 67.5 μg per mouse (2.5 mg / kg body weight), respectively. In addition, we compared two commonly used adjuvants, Freund's adjuvant and aluminum salts.

[0057] Lipid profile analysis showed that peptide immunization had no significant effect on serum cholesterol and serum LDL levels ( Figure 7 ).

[0058] See also Figure 7 It was found that peptide immunization had no significant effect on serum cholesterol and serum LDL levels.

[0059] Comparison of different doses of P1 and R1 peptide antigens in inhibiting atherosclerosis progression in apoE knockout mice by Oil Red O staining of whole-mount aorta

[0060] The animals' aortas were dissected and the effects of the peptides on atherosclerotic plaques were examined by whole-mount staining of the aorta with Oil Red O. Whole-mount staining of the aorta with Oil Red O is the most reliable of all analytical methods because it represents an unbiased representation of overall atherosclerosis progression.

[0061] KLH conjugated peptide P1 (HNERRVEWIFRGAVYQ) and peptide R1 (PHDGRLEWIFRRVLYR) were immunized into ApoE knockout mice. Two different doses of peptide antigens P1 and R1 were tried, 135 μg per mouse (5 mg / kg body weight) and 67.5 μg per mouse (2.5 mg / kg body weight), respectively. The results showed that at a dose of 67.5 μg per mouse (2.5 mg / kg body weight) and with aluminum salt as adjuvant ( Figure 8 A) or Freund's adjuvant ( Figure 8 C), both P1 and R1 reduced the progression of atherosclerosis. In addition, at a peptide dose of 135 μg per mouse (5 mg / kg body weight), both P1 and R1 reduced the progression of atherosclerosis in the presence of Freund's adjuvant ( Figure 8 D). Overall, the effect of P1 is slightly better than that of R1 ( Figure 8A, C, D), which is consistent with Figure 4 Note that since all peptides were conjugated to KLH, it is appropriate to use KLH as a control group.

[0062] Regarding the optimal dose, we found that 67.5 μg (2.5 mg / kg body weight) of P1 per mouse was at least equivalent to or even better than 135 μg (5 mg / kg body weight) per mouse for aluminum salts and Freund's adjuvant ( Figure 9 A). The results for peptide antigen R1 were similar to those for P1, with 67.5 μg per mouse (2.5 mg / kg body weight) being equivalent to or even superior to 135 μg per mouse (5 mg / kg body weight) for aluminum salt and Freund's adjuvant ( Figure 9 B). Comparison of two different adjuvants, aluminum salts and Freund's adjuvant, showed that Freund's adjuvant appeared to be slightly better than aluminum salts, and the difference between the two adjuvants was not statistically significant ( Figure 9 A and B).

[0063] Because the low dose of 67.5 μg per mouse (2.5 mg / kg body weight) was at least as effective as the high dose, we concluded that 67.5 μg per mouse (2.5 mg / kg body weight) was the optimal dose for antigen administration. Furthermore, aluminum salts and Freund's adjuvants performed equally well as adjuvants. Aluminum salts are not toxic to humans. Therefore, we selected aluminum salts as the more suitable adjuvant for future vaccine development.

[0064] Finally, we compared the effects of the optimal peptide antigen P1 with those of simvastatin at 10 mg / kg / day for 6 weeks, a currently used therapeutic agent. The results showed that P1 had a better anti-atherosclerotic effect than simvastatin ( Figure 10 ).

[0065] See also Figure 8 Both P1 and R1 reduced atherosclerotic progression. Furthermore, P1 was slightly more effective than R1. In most cases, P1 resulted in >10% improvement in reducing atherosclerotic lesion area.

[0066] See also Figure 10 It can be seen that P1 at a dose of 67.5 μg per mouse (2.5 mg / kg body weight) and 135 μg per mouse (5 mg / kg body weight) was more effective than simvastatin in reducing the area of ​​aortic atherosclerotic lesions.

[0067] Different doses of P1 and R1 peptide antigens were compared in inhibiting atherosclerosis progression in ApoE knockout mice as measured by thin tissue slide analysis of necrotic core size, Oil Red O staining, and MPO / CD68 staining.

[0068] The aortas of the animals were dissected, and the effects of the peptide on atherosclerotic plaques were examined by analyzing fibrosis and necrotic cores in aortic root tissue sections, as well as Oil Red O staining of whole-mount aortas and MPO / CD68 staining in aortic root tissue sections. Fibrosis and necrotic core size, as well as Oil Red O staining, indicate atherosclerosis progression. MPO and CD68 are markers of neutrophils and macrophages, which tend to accumulate in areas of atherosclerotic lesions.

[0069] The results showed that a high dose of 135 μg (5 mg / kg body weight) of P1 per mouse could reduce the size of the necrotic core in the presence of aluminum salts or Freund's adjuvant ( Figure 11 A low dose of 67.5 μg (2.5 mg / kg body weight) of P1 per mouse also reduced the size of the necrotic core in the presence of Freund's adjuvant ( Figure 11 On the other hand, a low dose of R1 of 67.5 μg (2.5 mg / kg body weight) per mouse could reduce the size of the necrotic core in the case of Freund's adjuvant when aluminum salt or Freund's adjuvant were used ( Figure 12 Even compared with simvastatin, P1 had a better effect in reducing the size of the necrotic core ( Figure 13 In the Oil Red O staining of aortic root tissue, P1 also reduced the Oil Red O-positive area ( Figure 14 In immunostaining of MPO (myeloperoxidase) and CD68, a high dose of 135 μg per mouse (5 mg / kg body weight) and a low dose of 67.5 μg per mouse (2.5 mg / kg body weight) of P1 reduced MPO staining, while having no significant effect on CD68 staining ( Figure 15 ).

[0070] See also Figure 11 It can be seen that compared with the control group immunized with KLH alone, at least when using Freund's adjuvant, P1 at doses of 67.5 μg per mouse (2.5 mg / kg body weight) and 135 μg per mouse (5 mg / kg body weight) could reduce the size of the necrotic core.

[0071] See also Figure 12 It was found that R1 at a dose of 67.5 μg per mouse (2.5 mg / kg body weight) could reduce the size of the necrotic core compared to the control group immunized with KLH alone when used with aluminum adjuvant or Freund's adjuvant.

[0072] See also Figure 13 It can be seen that P1 at a dose of 135 μg per mouse (5 mg / kg body weight) was more effective in reducing the size of the necrotic core than simvastatin treatment, at least in the case of Freund's adjuvant.

[0073] See also Figure 14 It can be seen that compared with the KLH control group, immunization with high and low doses of P1 reduced the progression of atherosclerosis in Oil Red O staining. Figure 6 Based on the results of section 2.ii, which showed the greatest effectiveness of P1 immunization, only P1 was investigated in the tissue section analysis.

[0074] See also Figure 15 It can be seen that compared with the KLH control group, immunization with a high dose of 135 μg per mouse (5 mg / kg body weight) and a low dose of 67.5 μg per mouse (2.5 mg / kg body weight) of P1 reduced MPO staining, while it had no significant effect on CD68 staining ( Figure 15 ).

[0075] The experimental part is summarized as follows:

[0076] 1) For atherosclerosis analysis, we used whole-mount Oil Red O staining of the aorta and thin tissue slide analysis of multiple indicators, including necrotic core size, Oil Red O staining, and MPO / CD68 staining. Of all these methods, whole-mount Oil Red O staining of the aorta is the most reliable because it represents an unbiased, global picture of atherosclerosis progression.

[0077] 2) Among all peptide antigens, P1 was the most effective in inhibiting atherosclerosis, and it was better than the KLH control group and simvastatin treatment.

[0078] 3) The effect of a low dose of 67.5 μg (2.5 mg / kg body weight) of P1 per mouse was at least as great as that of a high dose of 135 μg (5 mg / kg body weight) of P1 per mouse. Therefore, 67.5 μg (2.5 mg / kg body weight) per mouse is the optimal dose for antigen administration. Compared to the KLH control group, 67.5 μg (2.5 mg / kg body weight) of P1 per mouse reduced total atherosclerotic lesion area by 14% with aluminum salts and by 17% with Freund's adjuvant.

[0079] 4) Aluminum salts are as effective as Freund's adjuvants as adjuvants. Since aluminum salts are non-toxic to humans, they are a more suitable adjuvant for future vaccine development.

[0080] The vaccine formulation was tested in an ApoE mouse model using two different vaccine doses: 135 μg per mouse (5 mg / kg body weight) and 67.5 μg per mouse (2.5 mg / kg body weight). The dose used in ApoE knockout mice was determined based on the severity of atherosclerosis after feeding a high cholesterol diet, the animal's age, weight, general health, sex, time of administration, route of administration, and other similar factors well known in the medical field. When used in other species, including humans, the dose may need to be adjusted based on the aforementioned factors.

[0081] The background section of the present invention may contain background information about the problem or environment of the present invention, but does not necessarily describe the prior art. Therefore, the inclusion of content in the background section is not an admission by the applicant that the prior art is present.

[0082] The above description further details the present invention in conjunction with specific / preferred embodiments, and the specific implementation of the present invention should not be construed as being limited to these descriptions. Persons skilled in the art will appreciate that, without departing from the spirit of the present invention, they may make various substitutions or modifications to the described embodiments, and these substitutions or modifications should be considered to fall within the scope of protection of the present invention. Throughout this specification, reference to terms such as "one embodiment," "some embodiments," "preferred embodiments," "examples," "specific examples," or "some examples" indicates that the specific features, structures, materials, or characteristics described in conjunction with such embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of these terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Persons skilled in the art may combine and assemble the different embodiments or examples described in this specification, as well as features of different embodiments or examples, without conflicting opinions. Although the embodiments of the present invention and their advantages have been described in detail, it should be understood that various changes, substitutions, and modifications may be made herein without departing from the scope of protection of the patent application.

Claims

1. A peptide vaccine composition for reducing the progression of atherosclerosis, characterized in that Peptides comprising, alone or in combination, the E3 region of the TRPM2 ion channel derived from various species; specifically, peptide P1 based on a porcine sequence, or peptide R1 based on a rabbit sequence, or a combination of peptide R1 based on a rabbit sequence and peptide R2 based on a rabbit sequence, i.e., peptide R1+R2, for producing effective anti-TRPM2 polyclonal antibodies that can reduce the progression of atherosclerosis in an ApoE gene knockout mouse model, Among them, the peptide P1 based on the pig sequence is HNERRVEWIFRGAVYQ, Among them, the peptide R1 based on the rabbit sequence is PHDGRLEWIFRRVLYR, Among them, the peptide R2 based on the rabbit sequence is FGQIPLDEIDEARVNCSVH.

2. A pharmaceutical preparation, characterized in that Comprising the peptide vaccine composition according to claim 1 and an adjuvant.

3. The pharmaceutical preparation according to claim 2, wherein It is a pharmaceutical preparation administered by subcutaneous injection and is used as a vaccine to treat atherosclerosis.

4. The pharmaceutical preparation according to claim 2 or 3, wherein The adjuvant includes Freund's adjuvant and / or aluminum salt.

5. The pharmaceutical preparation according to any one of claims 2 to 3, characterized in that The peptide vaccine composition targets the E3 region of the TRPM2 ion channel.

6. Use of the peptide vaccine composition according to claim 1 for preparing a medicament for treating and preventing atherosclerosis.

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