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Fusion vaccine targeting immune checkpoint PD-L1 and for resisting pathogen infection

A PD-L1 and immune checkpoint technology, applied in the field of fusion vaccines targeting immune checkpoint PD-L1 for anti-pathogen infection, can solve the problem of high price of monoclonal antibodies, less pathogen-related disease prevention and control, and PD-L1 specificity Sexual antibody role is not clear and other issues

Active Publication Date: 2019-10-15
SHANGHAI VETERINARY RES INST CHINESE ACAD OF AGRI SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, monoclonal antibodies are expensive, immune checkpoint monoclonal antibodies such as PD-L1 are rarely used for the prevention and control of pathogen-related diseases, and the role of pre-existing PD-L1-specific antibodies is still unclear

Method used

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  • Fusion vaccine targeting immune checkpoint PD-L1 and for resisting pathogen infection
  • Fusion vaccine targeting immune checkpoint PD-L1 and for resisting pathogen infection
  • Fusion vaccine targeting immune checkpoint PD-L1 and for resisting pathogen infection

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Embodiment

[0034] Profilin (Pro) is an extremely important protein in parasites, which can assist parasites to invade host cells. Studies have shown that Pro can be used as a candidate vaccine against Babesia.

[0035] The present invention designs a vaccine targeting PD-L1, which is to fuse the PD-L1 Igv-like domain with the C-terminus of Pro, named Pro-PDL1E, and use it as a vaccine. The body's PD-L1-specific immune response was induced by active immunization, and its protective effect and mechanism of action in the mouse model infected by Babesia microti were evaluated. details as follows:

[0036] 1. Materials and methods

[0037] 1.1 Parasites and experimental animals

[0038] Babesia microti came from ATCCR PRA-99TM under the American Standard Culture Collection (ATCC), and was subcultured and preserved by BALC / c mice purchased from Shanghai Slack Experimental Animal Co., Ltd.

[0039] 1.2 Bacteria and plasmids

[0040] Escherichia coli DH5α (Invitrogen) and BL21(DE3) (Novagen)...

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Abstract

The invention discloses a fusion vaccine targeting an immune checkpoint PD-L1 and for resisting pathogen infection. The PD-L1Igv like domain is fused with the C-terminal of Pro, and the fusion vaccineis named as Pro-PDL1E. The fusion vaccine targeting the immune checkpoint PD-L1 and for resisting the pathogen infection has the following advantages that the Pro-PDL1E is induced to obtain a PD-L1 specific antibody, and the combining of PD-L1 and PD-1 in vitro is blocked; Pro-PDL1E reduces the burden of babesia microti in a mouse model, and PD-1 expression on T cells is reduced; and based on H&Estaining results, the Pro-PDL1E vaccine does not cause significant tissue damage. Moreover, the design strategy of the fusion vaccine targeting the immune checkpoint PD-L1 can be applied to the design of other vaccines targeting an autoimmune checkpoint and is a valuable strategy for animal vaccine design and adjuvant development with great potential.

Description

technical field [0001] The invention belongs to the technical field of vaccines, in particular to a fusion vaccine targeting immune checkpoint PD-L1 for anti-pathogen infection. Background technique [0002] Babesia is a type of protozoa that parasitizes large and small animals, including human erythrocytes, through blood-sucking transmission by ticks. Human infection cases have reached thousands in recent years, and they are distributed globally, including Britain, France, the United States, Germany, Switzerland, Sweden, Spain, Finland, Mexico and Ireland. More than 70 cases of Babesia infection have been found in Inner Mongolia, Xinjiang, Heilongjiang, Zhejiang, Shandong and Yunnan in my country. There are currently 4 species of Babesia and 3 unidentified species that can infect humans, including Babesia mircoti, B. divergens, B. duncani and Babesia orioni Bug (B. venatorum). Among them, Babesia microti is the main insect species causing human diseases. Now the babesio...

Claims

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Application Information

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IPC IPC(8): A61K39/018A61P33/02C12N15/62C12N15/70C07K19/00
CPCA61K39/018A61P33/02C07K14/70532C07K14/44C12N15/70A61K2039/575A61K2039/53C07K2319/00
Inventor 龚海燕蔺智兵韦娜娜陈兆国陆金苗
Owner SHANGHAI VETERINARY RES INST CHINESE ACAD OF AGRI SCI