A silica nanovaccine delivery platform templated by self-assembled antigen polypeptide fibers and construction and application thereof

Abstract

The present application relates to a kind of silica nanovaccine delivery platform with self-assembled polypeptide fiber as template and its construction and application.The present application nanovaccine delivery platform includes polypeptide fiber and silica, wherein polypeptide fiber is formed by antigen polypeptide monomer self-assembly, and polypeptide fiber is used as template to synthesize silica, and silica is wrapped in the surface of polypeptide fiber to form nanoparticle.The construction method of nanovaccine delivery platform includes the following steps:1) antigen polypeptide monomer is continuously incubated into polypeptide fiber;2) APTES is added to the reaction system of step 1) and continuously incubated;3) TEOS is added to the reaction system of step 2) and continuously incubated, and after continuous incubation, it is placed to age;4) the product of step 3) is centrifuged and washed.The nanovaccine constructed by the strategy can induce effective antigen-specific immune response to corresponding pathogen polypeptide.

Description

Technical Field

[0001] This invention relates to a silica nanovaccine delivery platform using self-assembled antigen peptide fibers as templates, and its construction and application. Specifically, it involves first assembling antigen peptides into nanofibers, and then using the nanofibers as templates to synthesize silica nanoparticles. This method can be used as a universal vaccine strategy for the prevention or treatment of various diseases. Background Technology

[0002] Peptide vaccines are a novel type of vaccine designed based on pathogen antigenic epitopes. They utilize chemically synthesized short peptides as antigens to elicit a specific immune response, showing broad application prospects in the immunotherapy of neurodegenerative diseases, cancer, infectious diseases, and autoimmune diseases. The core advantages of peptide vaccines are significant: high safety, containing only immunologically active short peptides without intact pathogen components, thus avoiding the risk of allergic reactions or autoimmune reactions; standardized preparation processes, facilitating large-scale synthesis, purification, storage, and transportation; and the ability to precisely target multiple pathogens or tumor antigens through multi-epitope design. However, peptide vaccines also have obvious drawbacks: as small molecules, short peptides are easily and rapidly decomposed after injection, resulting in weak immunogenicity, often requiring the use of appropriate adjuvants or delivery systems to enhance the immune response.

[0003] Current research has explored numerous strategies to enhance the immune response to peptide vaccines. For example, covalently modifying antigen peptide sequences with β-sheet-forming sequences can induce the modified peptides to self-assemble into nanofibers rich in β-sheet secondary structures. This self-assembly can serve as a self-delivery strategy, promoting antigen uptake by antigen-presenting cells (APCs) and facilitating APC maturation and activation. However, this strategy has drawbacks. The self-assembly of antigen peptides is highly dependent on their covalent coupling with β-sheet-forming exogenous sequences, and the introduction of such exogenous sequences can affect the presentation of antigenic epitopes, further impacting the efficacy and specificity of the immune response. Furthermore, the diverse intrinsic properties of peptides, such as surface charge and hydrophilicity / hydrophobicity, make selecting suitable universal adjuvants for these self-assembled fibers a challenge. Summary of the Invention

[0004] To address the two key scientific challenges of self-assembled peptide vaccines—dependence on exogenous sequences and difficulty in selecting suitable adjuvants—this invention provides a silica nanovaccine delivery platform using self-assembled antigen peptide fibers as templates, along with its construction and application. This nanovaccine delivery platform can synthesize silica through simple nucleation and growth using fibers formed by the self-assembly of various pathogen peptides as templates, thereby preparing a series of peptide vaccines capable of inducing strong and specific immune responses.

[0005] The purpose of this invention is to provide a silica nanovaccine delivery platform using self-assembled antigen peptide fibers as templates, comprising peptide fibers and silica, wherein the peptide fibers are formed by the self-assembly of antigen peptide monomers, and silica is synthesized using the peptide fibers as templates, the peptide fibers serve as antigens, the nano silica serves as vaccine adjuvants, and the silica is coated on the surface of the peptide fibers to form nanoparticles.

[0006] Furthermore, the types of antigenic peptides include, but are not limited to, Alzheimer's disease antigenic peptides (e.g., Aβ42), or Alzheimer's disease-related proteins (e.g., Tau protein) or sequence fragments thereof, human papillomavirus antigenic peptides (e.g., E6 and E7) or sequence fragments thereof, varicella-zoster virus antigenic peptides, varicella-zoster virus proteins (e.g., gE protein) or sequence fragments thereof, and influenza virus antigenic peptides (e.g., M2e) or sequence fragments thereof.

[0007] Furthermore, the width of the polypeptide fiber (antigen polypeptide self-assembled into fiber) is 2-100 nm, preferably 10-20 nm.

[0008] Furthermore, the vaccine is a nanoparticle with a width of 10-500 nm, preferably 10-100 nm.

[0009] Furthermore, the mass ratio of silicon to polypeptide (antigen polypeptide fiber) in the nano-vaccine is 50-0.1:1, preferably 20-0.25:1, and more preferably 10-0.5:1.

[0010] Another objective of this invention is to provide the application of the silica vaccine delivery platform constructed using self-assembled antigenic polypeptide fibers as templates in various preventive and therapeutic vaccines, and to construct corresponding Alzheimer's disease vaccines, human papillomavirus vaccines, shingles vaccines, influenza virus vaccines, and other vaccines based on the above-mentioned various antigenic polypeptides.

[0011] Another object of the present invention is to provide a method for constructing the above-mentioned silica nanovaccine delivery platform using self-assembled antigen polypeptide fibers as templates, the method comprising the following steps: 1) The antigen polypeptide monomer is continuously incubated into polypeptide fibers; 2) Add 3-aminopropyltriethoxysilane (APTES) to the reaction system of step 1) and incubate continuously; 3) Add tetraethoxysilane (TEOS) to the reaction system of step 2) and incubate continuously, followed by static aging; 4) Centrifuge and wash the product obtained in step 3) to obtain the nano-vaccine.

[0012] Further, the concentration of the antigenic polypeptide monomer (e.g., Aβ42) in the reaction system in step 1) is 10-1000 μM, preferably 50-500 μM, more preferably 50-200 μM; or the concentration of the antigenic polypeptide monomer (e.g., E6, E7) in the reaction system in step 1) is 10-1000 ug / mL, preferably 50-500 ug / mL, more preferably 100-300 ug / mL.

[0013] Further, in step 2), the ratio of APTES to the reaction system is 0.025-2.000:500 (v:v), preferably 0.025-1.000:500 (v:v), and more preferably 0.1-0.5 / 500 (v:v).

[0014] Further, in step 3), the ratio of TEOS to the reaction system is 0.5-40.0:500 (v:v), preferably 0.5-20.0:500 (v:v), and more preferably 2.5-10.0:500 (v:v).

[0015] Further, in step 1), the incubation speed is 100-500 rpm, preferably 200-400 rpm; the incubation time is 0.5-24 hours, preferably 1.0-16 hours, more preferably 2-12 hours; the incubation pH is 5.0-9.0, preferably 6.0-8.0, more preferably 6.5-7.5; and the incubation is carried out in HEPES buffer.

[0016] Further, in step 2), the incubation speed is 300-1500 rpm, preferably 600-1200 rpm, the incubation time is 2-30 minutes, preferably 5-30 minutes, and the incubation pH is 5.0-9.0, preferably 6.0-8.0, preferably 6.5-7.5.

[0017] Further, in step 3), the incubation speed is 300-1500 rpm, preferably 600-1200 rpm, the incubation time is 5-60 minutes, preferably 15-60 minutes; the incubation pH is 5.0-9.0, preferably 6.0-8.0, preferably 6.5-7.5; and the aging time is 1-12 hours, preferably 1-6 hours.

[0018] Furthermore, the incubation and static aging temperatures in steps 1) to 3) are 4-50°C, preferably 4-30°C.

[0019] Furthermore, the solvent used for centrifugal washing in step 4) is water.

[0020] Furthermore, all samples prepared in steps 1), 2), 3), and 4) are prepared fresh for immediate use.

[0021] Furthermore, repeating steps 2)-4) can be used to increase the Si content in the nano-vaccine, with the number of repetitions being 1.

[0022] Furthermore, when repeating the operation, the reaction system is water or HEPES buffer, and the pH value of the HEPES buffer is 5.0-9.0, preferably 6.0-8.0, and more preferably 6.5-7.5.

[0023] Furthermore, during repeated operations, the concentration of the nano-vaccine in the reaction system is 100-1000 μg / mL, preferably 250-450 μg / mL.

[0024] The beneficial effects of this invention are: The silica vaccine of this invention, which uses self-assembled antigenic polypeptide fibers as templates, can induce an effective antigen-specific immune response against the corresponding pathogenic polypeptides. In vivo experiments in mice have verified that it can induce good immunotherapeutic effects against different diseases.

[0025] The preparation method of the nanovaccine delivery platform described in this invention, which can induce strong immunotherapeutic effects for different diseases, is simple, easy to operate, has good reproducibility, and mild reaction conditions. The final product is a vaccine nanoparticle with uniform dispersion, uniform particle size, and good stability, which has good application prospects in the prevention and treatment of diseases. Attached Figure Description

[0026] Figure 1 This is a schematic diagram illustrating the synthesis mechanism of the nanovaccine (SiO2@Aβ42 fibril) synthesized in Example 1, which uses Aβ42 polypeptide self-assembled fiber (Aβ42 fibril) as the antigen and silica as the adjuvant synthesized using the fiber as a template.

[0027] Figure 2 Transmission electron microscopy (TEM) images of Aβ42 fibril and SiO2@Aβ42 fibril, with a scale bar of 500 nm.

[0028] Figure 3 The image shows the energy-dispersive X-ray spectrum (EDS) of SiO2@Aβ42 fibril, where red represents Si, green represents O, and yellow represents the co-location of Si and O. The scale bar is 500 nm.

[0029] Figure 4 TEM image of Secondary SiO2@Aβ42 fibril nanovaccines, with a scale bar of 500 nm.

[0030] Figure 5 The therapeutic effect of Secondary SiO2@Aβ42 fibril nanovaccines on APP / PS1 transgenic mice. Here, A represents the results of the hindlimb clamping test; B represents the results of the nesting test; and C represents the results of the novel object recognition test. ns indicates p > 0.05. This means p < 0.05. This means p < 0.01. This means p < 0.001. 1 represents p < 0.001; D represents the experimental results of brain Aβ42 clearance, where the scale bar is 100 μm.

[0031] Figure 6 TEM images of E7 fibril, SiO2@E7 fibril, and Secondary SiO2@E7 fibril, with a scale bar of 500 nm.

[0032] Figure 7 The therapeutic effect of Secondary SiO2@E7 fibril nanovaccines on TC-1 tumor-bearing mice. Where A represents the tumor growth rate of the mice; B represents the survival rate of the mice; and C represents the CD8+ of the spleen. + T cells in CD3 + The proportion of T cells; D represents spleen FasL. + Cells in CD8 + The proportion of T cells; E represents tumor tissue FasL + Cells in CD8 + The proportion of T cells, where ns represents p>0.05. This means p < 0.05. This means p < 0.01. This means p < 0.001. Detailed Implementation

[0033] The following non-limiting embodiments are intended to enable those skilled in the art to fully understand the invention, but are not intended to limit the invention in any way.

[0034] Example 1 A method for constructing a nanovaccine (SiO2@Aβ42 fibril) using self-assembled β-amyloid protein (1-42) (Aβ42) polypeptide fibers as antigens and silica as an adjuvant synthesized using these fibers as templates (e.g.) Figure 1 As shown), the method includes the following steps: 1) Aβ42 self-assembled nanofibers (Aβ42 fibril) were prepared by incubating 200 μM Aβ42 polypeptide monomer (purity >95%, purchased from Jier Biochemical (Shanghai) Co., Ltd.) at 300 rpm and 37°C for 12 hours in a 10 mM HEPES buffer solution with pH=7.0. 2) Add APTES to the reaction system of step 1) at a ratio of 0.5:500 (v:v) and incubate continuously at 1000 rpm and 25°C for 15 minutes to obtain APTES@Aβ42 fibril; 3) Add TEOS to the reaction system in step 2) at a ratio of 10.0:500 (v:v), incubate continuously at 1000 rpm and 25°C for 30 minutes, and then let the incubated reaction system stand at 25°C for 3.5 hours. 4) Wash the product from step 3) with ultrapure water by centrifugation to obtain the nano-vaccine (SiO2@Aβ42 fibril).

[0035] Example 2 The physicochemical properties of the Aβ42 self-assembled nanofibers (Aβ42 fibril) prepared in Example 1 and the silica-adjuvanted nanovaccine (SiO2@Aβ42 fibril) synthesized using Aβ42 as a template were analyzed. 1) The morphology of Aβ42 fibril and SiO2@Aβ42 fibril was detected using transmission electron microscopy (TEM) (e.g., Figure 2 As shown in the figure), TEM results indicate that Aβ42 fibril possesses a typical fiber morphology, while SiO2@Aβ42 fibril exhibits a morphology of nanoparticles encapsulating fibers. Their widths were quantified using TEM images (as shown in Table 1). 2) Elemental distribution maps of Si and O in SiO2@Aβ42 fibril were detected by energy-dispersive X-ray spectroscopy (EDS) (e.g., Figure 3 As shown in the figure, the EDS results indicate that Si and O elements are co-located, proving the formation of silica along the fiber surface; 3) The hydrodynamic dimensions, polydispersity index (PDI), and zeta potential of Aβ42 fibril and SiO2@Aβ42 fibril in deionized water were quantified by dynamic light scattering (DLS) (as shown in Table 1). 4) The Aβ42 content in SiO2@Aβ42 fibril was quantified by the Aβ42 concentration of the supernatant in the washing step of Example 1. Furthermore, the Si element in Aβ42 fibril and SiO2@Aβ42 fibril was quantified by inductively coupled plasma optical emission spectrometry (ICP-OES) to obtain the mass ratio of Si and O elements in Aβ42 fibril and SiO2@Aβ42 fibril (as shown in Table 1).

[0036] Table 1

[0037] Example 3 To increase the Si content in the SiO2@Aβ42 fibril nanovaccine, the SiO2@Aβ42 fibril prepared in Example 1 was incubated with APTES and TEOS to prepare Secondary SiO2@Aβ42 fibril, specifically including the following steps: 1) The SiO2@Aβ42 fibril prepared in Example 1 was dispersed in deionized water and then ultrasonically dispersed evenly in an ice-water bath. The concentration of SiO2@Aβ42 fibril was 409 μg / mL. 2) Add APTES to the reaction system of step 1) at a concentration of 0.25:500 (v:v) and incubate continuously for 15 minutes at a speed of 1000 rpm and a temperature of 25°C; 3) Add TEOS to the reaction system of step 2) at a concentration of 5.0:500 (v:v) and incubate continuously at 1000 rpm and 25°C for 30 minutes. Then let the incubated reaction system stand at 25°C for 3.5 hours. 4) Wash the product from step 3) with ultrapure water by centrifugation to obtain the nano-vaccine (Secondary SiO2@Aβ42fibril).

[0038] The morphology of Secondary SiO2@Aβ42 fibril was detected using TEM (e.g., Figure 4The widths of the secondary SiO2@Aβ42 fibril in deionized water were quantified using TEM images (as shown in Table 2). The hydrodynamic dimensions, PDI, and Zeta potential of the secondary SiO2@Aβ42 fibril in deionized water were quantified using DLS (as shown in Table 2). The Aβ42 content in the secondary SiO2@Aβ42 fibril was quantified using the Aβ42 concentration in the supernatant during the washing steps. Furthermore, the Si element in the secondary SiO2@Aβ42 fibril was quantified using ICP-OES, thus obtaining the mass ratio of Si to O elements in the secondary SiO2@Aβ42 fibril (as shown in Table 2).

[0039] Table 2

[0040] Example 4 Using 7-month-old female transgenic APP / PS1 mice (purchased from Liaoning Changsheng Biotechnology Co., Ltd.) with Alzheimer's disease as an animal model, the immunotherapeutic efficacy of the Secondary SiO2@Aβ42 fibril nanovaccine in Example 3 was tested. The method included the following steps: At week 0, mice were subcutaneously injected with 100 μL of saline containing the Secondary SiO2@Aβ42 fibril nanovaccine prepared in Example 3 (containing 22.5 μg of Aβ42 and 467.2 μg of SiO2). At weeks 2, 4, and 6, mice were injected again with the same dose of saline containing the Secondary SiO2@Aβ42 fibril nanovaccine (Treated APP / PS1 group). At weeks 10-12, behavioral and immune response assessments were performed on the mice, including hindlimb clamping test, nesting test, new object recognition test, and detection of brain Aβ42 levels. Untreated female, age-matched, non-transgenic wild-type C57BL / 6 mice (WT group) and untreated APP / PS1 mice (APP / PS1 group) served as the control group for this experiment, with 6 mice in each group.

[0041] The results of the mouse hindlimb clamping test, nesting test, novel object recognition test, and brain Aβ42 level detection are as follows: Figure 5 As shown.

[0042] like Figure 5As shown in Example 3, the results indicated that the hindlimb clamping test scores of wild-type mice and untreated APP / PS1 mice were 0.00±0.00 and 2.17±0.90, respectively (representing that the lower the score, the more complete the motor function). After treatment with Secondary SiO2@Aβ42 fibril, the hindlimb clamping test score of APP / PS1 mice decreased to 0.50±0.76, indicating that the motor deficit of APP / PS1 mice had been significantly improved. The nesting test scores of wild-type mice and untreated APP / PS1 mice were 3.83±0.37 and 1.50±0.50, respectively (representing that the higher the score, the more complete the cognitive ability). After treatment with Secondary SiO2@Aβ42 fibril, the nesting test score of APP / PS1 mice increased to 2.67±0.75, indicating that the cognitive function of APP / PS1 mice had been significantly improved. The new object recognition times for wild-type mice and untreated APP / PS1 mice were 16.95±3.40 seconds and 9.50±2.80 seconds, respectively (representing that longer new object recognition times indicate better short-term memory). After treatment with Secondary SiO2@Aβ42 fibril, the new object recognition time in APP / PS1 mice increased to 16.46±3.06 seconds, indicating a recovery in short-term memory. Immunohistochemistry (IHC) analysis of Aβ42 levels in the mouse brain showed that Secondary SiO2@Aβ42 fibril treatment significantly reduced Aβ42 levels in the brains of APP / PS1 mice, indicating significant clearance of Aβ42 plaques. In conclusion, Secondary SiO2@Aβ42 fibril can restore motor function and cognitive deficits in APP / PS1 mice and clear Aβ42 plaques in their brains.

[0043] Example 5 Following the construction approach of SiO2@Aβ42 fibril nanovaccine, human papillomavirus E7 peptides (49-57) were self-assembled into E7 fibril, and SiO2@E7 fibril nanovaccine was constructed based on E7 fibril. The method includes the following steps: 1) E7 self-assembled nanofibers (E7 fibril) were prepared by incubating E7 polypeptide monomer (purity 98%, purchased from Nanjing Genscript Biotech Co., Ltd.) at a concentration of 200 μg / mL at a temperature of 37°C for 2 hours at a speed of 300 rpm. The incubation system was 10 mM HEPES buffer at pH=7.0. 2) Add APTES to the reaction system of step 1) at a ratio of 0.25:500 (v:v) and incubate continuously at 1000 rpm and 25°C for 15 minutes. 3) Add TEOS to the reaction system of step 2) at a concentration of 5.0:500 (v:v) and incubate continuously at 1000 rpm and 25°C for 30 minutes. Then let the incubated reaction system stand at 25°C for 3.5 hours. 4) Wash the product from step 3) with ultrapure water by centrifugation to obtain the nano-vaccine (SiO2@E7 fibril).

[0044] Example 6 To increase the Si content in SiO2@E7 fibril nano-vaccines, secondary SiO2@E7 fibril was prepared by incubating it with APTES and TEOS. The specific steps included: 1) The SiO2@E7 fibril prepared in Example 5 was dispersed in deionized water and then ultrasonically dispersed evenly in an ice-water bath. The concentration of SiO2@E7 fibril was 267 μg / mL. 2) Add APTES to the reaction system of step 1) at a ratio of 0.13:500 (v:v) and incubate continuously at 1000 rpm and 25°C for 15 minutes; 3) Add TEOS to the reaction system in step 2) at a ratio of 2.5:500 (v:v), incubate continuously at 1000 rpm and 25°C for 30 minutes, and then let the incubated reaction system stand at 25°C for 3.5 hours. 4) Wash the product from step 3) with ultrapure water by centrifugation to obtain the nano-vaccine (Secondary SiO2@E7fibril).

[0045] Example 7 The morphology of E7 fibril, SiO2@E7 fibril and Secondary SiO2@E7 fibril in Examples 5-7 was detected using TEM (e.g., Figure 6As shown in the figure, TEM results show that E7 fibril has a typical fiber morphology. Both SiO2@E7fibril and Secondary SiO2@E7fibril have a morphology of nanoparticles encapsulating fibers, and the size of Secondary SiO2@E7fibril is wider. Their widths were quantified by TEM images (as shown in Table 3); the hydrodynamic size, polydispersity index (PDI), and zeta potential of E7 fibril, SiO2@E7fibril, and Secondary SiO2@E7fibril in deionized water were quantified by DLS (as shown in Table 3); the Si element in E7 fibril, SiO2@E7fibril, and Secondary SiO2@E7fibril was quantified by ICP-OES, and their Si to O element mass ratios were obtained (as shown in Table 3).

[0046] Table 3

[0047] Example 8 Using 6-8 week old tumor-bearing C57BL / 6 mice (female, purchased from Liaoning Changsheng Biotechnology Co., Ltd.) as an animal model, the immunotherapeutic efficacy of the Secondary SiO2@E7 fibril nanovaccine in Example 5 was verified. The method included the following steps: On day 0, TC-1 cells (purchased from Stemer (Shanghai) Biotechnology Co., Ltd.) were subcutaneously injected into the right abdomen of the mice, with a cell count of 2 × 10⁶ cells. 5 On days 5, 12, and 19, mice were injected intramuscularly with 100 μL of saline containing the Secondary SiO2@E7 fibril nanovaccine prepared in Example 7 (containing 10 μg of E7 and 160 μg of SiO2). Immune response was assessed on day 33, and tumor volume and survival rate (tumor volume > 2000 mm²) were evaluated throughout the experimental period. 3 The mice were then euthanized. Mice injected with an equal dose of saline (Ctrl group) and mice injected with an equal dose of E7 fibril (E7 fibril group) served as the control group for this experiment, with 8 mice in each group.

[0048] Tumor growth kinetics and survival rate in mice, such as Figure 7 As shown in AB.

[0049] Immune responses in mouse spleen and tumor tissue, such as Figure 7 As shown in CE.

[0050] like Figure 7 As shown in AB, the results of Example 4 demonstrate that treatment with Secondary SiO2@E7 fibril significantly slowed tumor growth in TC-1 tumor-bearing mice and significantly improved their survival rate; Figure 7 As shown in CE, the results of Example 6 indicate that treatment with Secondary SiO2@E7 fibril can induce significant CD8 production in the spleen of mice. + T cell and CTL responses were observed, and a significant CTL immune response was induced in tumor tissues of mice. In summary, Secondary SiO2@E7fibril demonstrated good immunotherapeutic effects in TC-1 tumor-bearing mice.

[0051] This invention has constructed two nano-vaccines (SiO2@Aβ42 fibril and SiO2@E7 fibril) using the above-mentioned vaccine system, both of which have shown good immunotherapeutic efficacy.

Claims

1. A silica nanovaccine delivery platform using self-assembled antigen polypeptide fibers as templates, characterized in that: It includes peptide fibers and silica. The peptide fibers are formed by the self-assembly of antigen peptide monomers, and silica is synthesized using the peptide fibers as templates. The silica is then coated on the surface of the peptide fibers to form nanoparticles.

2. The silica nanovaccine delivery platform based on self-assembled antigen polypeptide fibers as a template, as described in claim 1, is characterized in that: The antigenic polypeptides include: Alzheimer's disease antigenic polypeptides, or proteins or sequence fragments thereof associated with Alzheimer's disease, human papillomavirus antigenic polypeptides or sequence fragments thereof, varicella-zoster virus antigenic polypeptides, varicella-zoster virus proteins or sequence fragments thereof, and influenza virus antigenic polypeptides or sequence fragments thereof.

3. The silica nanovaccine delivery platform using self-assembled antigen polypeptide fibers as templates according to claim 2, characterized in that: The Alzheimer's disease antigen peptide is Aβ42, the human papillomavirus antigen peptide is E6 or E7, the varicella-zoster virus protein is gE protein, and the influenza virus antigen peptide is M2e.

4. The silica nanovaccine delivery platform using self-assembled antigen polypeptide fibers as templates according to claim 1, characterized in that: The width of the polypeptide fiber is 2-100 nm, and the width of the nanovaccine is 10-500 nm.

5. The silica nanovaccine delivery platform using self-assembled antigen polypeptide fibers as templates according to claim 1, characterized in that: The mass ratio of silicon to peptides in the nano-vaccine is 50-0.1:

1.

6. The application of the silica nanovaccine delivery platform based on self-assembled antigen polypeptide fibers as a template, as described in any one of claims 1-5, in preventive and therapeutic vaccines.

7. A method for constructing a silica nanovaccine delivery platform using self-assembled antigen polypeptide fibers as a template, as described in any one of claims 1-5, characterized in that: Includes the following steps: 1) The antigen polypeptide monomer is continuously incubated into polypeptide fibers; 2) Add 3-aminopropyltriethoxysilane to the reaction system of step 1) and incubate continuously; 3) Add tetraethoxysilane to the reaction system of step 2) and incubate continuously, followed by static aging; 4) Centrifuge and wash the product from step 3) to obtain the nano-vaccine.

8. The construction method according to claim 7, characterized in that: The concentration of the antigenic polypeptide in step 1) in the reaction system is 10-1000 μM or 10-1000 ug / mL; In step 2), the volume ratio of 3-aminopropyltriethoxysilane to the reaction system is 0.025-2.000:500; In step 3), the volume ratio of tetraethoxysilane to the reaction system is 0.5-40.0:

500.

9. The construction method according to claim 7, characterized in that: In step 1), the incubation speed is 100-500 rpm, the incubation time is 0.5-24 hours, and the incubation pH is 5.0-9.0, preferably 6.0-8.

0. The incubation speed in step 2) is 300-1500 rpm, and the incubation time is 2-30 minutes; In step 3), the incubation speed is 300-1500 rpm, the incubation time is 5-60 minutes, and the aging time is 1-12 hours. The incubation and static aging temperatures in steps 1) to 3) are 4-50℃; The solvent used for centrifugal washing in step 4) is water.

10. The construction method according to claim 7, characterized in that: Repeat steps 2)-4).

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