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Application of fluorinated polyethyleneimine in preparation of vaccine or preparation for preventing/treating diseases caused by viruses/bacteria

A technology of fluorinated polyethyleneimine and branched polyethyleneimine, which is applied in antiviral agents, antibacterial drugs, antibody medical components, etc., can solve the problem of lack of individualized curative effect prediction targets, endangering patients' lives, and declining vitality To achieve a strong immune memory effect and enhance the effect of antigen-specific T cell immune response

Pending Publication Date: 2022-03-15
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Nevertheless, there are still many unresolved problems in the field of tumor immunotherapy: for example, immunotherapy lacks individualized curative effect prediction targets; T lymphocytes, the main force of immunotherapy, generally have problems such as decreased vitality, immune tolerance, and functional exhaustion; Patients have clinically relevant phenomena such as "false positive" and "false positive" after immunotherapy; in addition, while CAR-T kills tumor cells, it can produce a large number of inflammatory factors, triggering cytokine storms, etc., which endanger the lives of patients problems, tumor immunotherapy still needs to be further improved
Although some nanocarriers have achieved the loading and delivery of antigens and adjuvants, there are also certain defects: in the existing nanovaccine, there are not many nanomaterial carriers with adjuvant function.
However, in view of the higher requirements of tumor immunotherapy, there are currently no reports on the use of fluorinated polyethyleneimine (F-PEI) for vaccine delivery and immune adjuvant applications

Method used

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  • Application of fluorinated polyethyleneimine in preparation of vaccine or preparation for preventing/treating diseases caused by viruses/bacteria
  • Application of fluorinated polyethyleneimine in preparation of vaccine or preparation for preventing/treating diseases caused by viruses/bacteria
  • Application of fluorinated polyethyleneimine in preparation of vaccine or preparation for preventing/treating diseases caused by viruses/bacteria

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] Embodiment 1: the construction of the nano-vaccine based on F-PEI

[0057] figure 1 It is a schematic diagram of the construction process of the nano vaccine, and the specific steps are as follows:

[0058] Mix F-PEI and OVA in an aqueous solution at room temperature and incubate for 5 to 30 minutes to obtain F-PEI / OVA nanovaccine

[0059] Specifically, F-PEI is F 7 -PEI or F 13 -PEI, its structural formula is as follows:

[0060]

[0061] Among them, R is a group with the following structural formula (the * mark represents the group connection site):

[0062]

[0063] Among them, F 7 - n of PEI is 2, F 13 -n is 5 for PEI. f 7 -PEI and F 13 - In PEI, x is 30 and 27. f 7 -PEI and F 13 - m in PEI is 46, that is, the molecular weight of the branched polyethyleneimine is 25 kDa.

[0064] Different nano-vaccines were prepared by changing the mass ratio of F-PEI to OVA. Table 1 shows the dynamic light scattering results of the F-PEI-based nano-vaccine cons...

Embodiment 2

[0068] Example 2: F-PEI can induce OVA-specific T cell immune response

[0069] The immunological evaluation plan is as follows:

[0070] The mice were injected with the nano-vaccine prepared in Example 1, and the lymph nodes were excised on the 3rd and 5th days after the injection, and the spleen was excised on the 7th day for immune evaluation.

[0071] Depend on image 3 As shown in a, b, c, F 13 -PEI / OVA nanovaccine can significantly induce the maturation of DC cells in vivo. And on the 5th day after vaccination, F 13 -More DC cells that induce antigen cross-presentation were detected in mice with PEI / OVA nanovaccine. Proof F 13 -PEI / OVA nanovaccine can induce innate immune response and can enhance antigen cross-presentation.

[0072] We then investigated whether OVA-specific adaptive immune responses were induced in mice. Depend on image 3 As shown in d and e, on the 7th day after vaccination, the OVA-specific IgG2a and IgG1 in mouse serum were detected by ELISA ...

Embodiment 3

[0074] Embodiment 3: The preventive effect of F-PEI / OVA nano-vaccine to B16-OVA melanoma

[0075] Respectively with saline (Blank), OVA, F 7 -PEI / OVA or F 13 -PEI / OVA intradermally immunized C57 / BL6 mice 3 times at intervals of 7 days. B16-OVA melanoma cells expressing OVA were injected 7 days after the last immunization.

[0076] like Figure 4 As shown, injected with F 13 -The average tumor volume of PEI / OVA nano-vaccine in mice inoculated with B16-OVA for 21 days was significantly smaller than that of other groups ( Figure 4 a) and inoculated with F 13 -The survival time of mice with PEI / OVA nanovaccine was significantly prolonged ( Figure 4 b).

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Abstract

The invention relates to application of fluorinated polyethyleneimine in preparation of vaccines or preparations for preventing / treating diseases caused by viruses / bacteria. The invention discloses a novel application of fluorinated polyethyleneimine, which provides an intracellular delivery system for enhancing vaccine delivery efficiency and enhancing antigen-specific immunoreaction, and the fluorinated polyethyleneimine can be used as an antigen carrier and can play a role of an immunologic adjuvant at the same time.

Description

technical field [0001] The invention relates to the field of biological preparations, in particular to the application of fluorinated polyethyleneimine in the preparation of vaccines or preparations for preventing / treating diseases caused by viruses / bacteria. Background technique [0002] In the 21st century, with the continuous development and cross penetration of oncology, immunology, cell biology, biochemistry and molecular biology, the theoretical basis and clinical research of tumor immunotherapy have achieved rapid development. So far, tumor immunotherapy methods include tumor vaccines, immune checkpoint (ICB) monoclonal antibodies, and cellular immunotherapy. Among them, cellular immunotherapy represented by chimeric antigen receptor (CAR) T cells has achieved a complete remission rate of 90%. Immunotherapy represented by immune checkpoint antibodies has achieved good results in melanoma, lymphoma, non-small cell lung cancer, and has been approved by the US Food and ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/385A61K39/39A61P31/04A61P31/12A61P35/00A61P35/04
CPCA61K39/39A61P31/12A61P31/04A61P35/00A61P35/04A61K39/385A61K2039/55555A61K2039/575A61K2039/57A61K2039/6093
Inventor 刘庄彭睿徐骏程义云
Owner SUZHOU UNIV
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