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Application of PDL1-IgGFc fusion protein in inhibition of severe malaria morbidity

A fusion protein, PD-1 technology, applied in the direction of fusion polypeptides, peptide/protein components, resistance to vector-borne diseases, etc., can solve problems such as incomplete elucidation, and achieve the effect of prolonging survival time and relieving cerebral malaria

Active Publication Date: 2016-10-12
FOURTH MILITARY MEDICAL UNIVERSITY
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Problems solved by technology

But up to now, the specific mechanism of blood-brain barrier damage in cerebral malaria has not been fully elucidated.

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  • Application of PDL1-IgGFc fusion protein in inhibition of severe malaria morbidity
  • Application of PDL1-IgGFc fusion protein in inhibition of severe malaria morbidity
  • Application of PDL1-IgGFc fusion protein in inhibition of severe malaria morbidity

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Embodiment Construction

[0033] The present invention will be further described in detail below in conjunction with specific embodiments, which are explanations of the present invention rather than limitations.

[0034] The pre-experimental results of the present invention in the mouse model of PD-1 gene knockout cerebral malaria have proved that the regulation of the PD-1 / PD-L pathway has a significant impact on the outcome of cerebral malaria, which makes it possible to properly up-regulate PD- The 1 / PD-L pathway makes possible an immunotherapy strategy to alleviate the symptoms of severe malaria such as cerebral malaria.

[0035] Based on the above research results, the present invention puts forward the following hypothesis: if vascular endothelial cells can specifically overexpress PD-L ligands in the mouse cerebral malaria model, then CD8+ CTL cells will receive more PD from endothelial cells. -L signal, more PD-1 receptors on the surface will be activated, thereby transducing more inhibitory si...

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Abstract

The invention discloses an application of a PDL1-IgGFc fusion protein in inhibition of severe malaria morbidity, and belongs to the technical field of anti-malaria drug preparation. A fusion gene of a PDL1 molecule extracellular fragment and an IgG molecule Fc fragment is constructed, the fusion gene is constructed into adenovirus or is expressed in vitro, and the fusion protein is verified to be successfully expressed by a Western Blot method. In in-vitro cell experiments, the fusion protein can significantly inhibit ConA induced CD8+T cell activation; at the same time, in mice in-vivo cell experiments, through caudal vein injection of recombinant adenovirus for expressing the PDL1-IgGFc fusion protein, occurrence of cerebral malaria caused by infection of a plasmodium berghei ANKA strain can be significantly alleviated, and the survival time of mice is prolonged. The PDL1-IgGFc fusion protein is indicated to have a role in inhibiting severe malaria morbidity, and the inhibition role is involved with inhibition of CD8+T cell activation. The fusion protein provides a new drug selection for treatment of cerebral malaria and other severe malaria in clinic.

Description

technical field [0001] The invention belongs to the technical field of preparation of antimalarial drugs, and in particular relates to the application of PDL1-IgGFc fusion protein to inhibit severe malaria. Background technique [0002] Malaria is one of the most prevalent infectious diseases in the world, threatening 3.2 billion people worldwide. In 2014, there were approximately 214 million malaria cases and 440,000 deaths worldwide. There are five main species of Plasmodium that infect humans. Severe malaria is usually caused by Plasmodium falciparum. Among them, cerebral malaria is one of the most serious severe malaria. Studies have pointed out that even after active treatment, its mortality rate can still be as high as 18%. Most children with cerebral malaria die within 1-2 days after the onset of central nervous system symptoms, and even surviving cases often have neurological sequelae. Most studies believe that cerebral malaria is caused by the adhesion of erythrocy...

Claims

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Application Information

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IPC IPC(8): A61K38/17C07K19/00C12N15/62A61P33/06
CPCA61K38/17C07K14/435C07K2319/30Y02A50/30
Inventor 赵亚王军沈燕李英辉梁姣黄豫晓
Owner FOURTH MILITARY MEDICAL UNIVERSITY
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