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Application of poly inosine-cytidine, imiquimod and gardiquimod in constructing virus immunity mouse model

A technology of polyinosinic acid and immunizing mice, applied in the field of constructing virus immunization mouse models

Inactive Publication Date: 2017-05-31
宁波美丽人生医药生物科技发展有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Furthermore, the deleterious effects of polyinosinic acid may be mediated by type I interferons

Method used

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  • Application of poly inosine-cytidine, imiquimod and gardiquimod in constructing virus immunity mouse model
  • Application of poly inosine-cytidine, imiquimod and gardiquimod in constructing virus immunity mouse model
  • Application of poly inosine-cytidine, imiquimod and gardiquimod in constructing virus immunity mouse model

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Polyinosinic acid reduces bacterial clearance

[0053] We first examined the effect of polyinosinic acid administration on bacterial clearance following bacterial infection. The experimental animals were given intranasal administration of polyinosinic acid or imiquimod for two consecutive days (ie, twice). On the third day (i.e., 24 hours after the last polyinosinic acid dose), animals were injected with S. pneumoniae intrathecally. We found a significant increase in bacterial counts in the lungs of animals administered nasal polyinosinic acid. Interestingly, imiquimod or gademotel (TLR7 agonists such as figure 1 A) There was no significant difference in bacterial clearance between the treatment groups. But both groups showed robust clearance during the initial challenge phase. Administration of TLR7 ligand alone was therefore not sufficient to reduce bacterial clearance.

[0054] Second, we examined whether polyinosinic acid also reduced the clearance of another i...

Embodiment 2

[0056] Polyinosinic acid increases susceptibility of lung tissue to bacteria

[0057] Second, we examined whether polyinosinic acid also reduced the clearance of another important clinical pathogen, methicillin-resistant Staphylococcus aureus (MRSA), causing viral secondary bacterial pneumonia. Similar to the above category, after 24h of Staphylococcus aureus infection, polyinosinic acid administration will reduce its clearance rate ( figure 1 B). Thus, polyinosinic acid appears to impair host lung tissue defense mechanisms against two pathogens clinically responsible for viral secondary bacterial pneumonia, Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus.

Embodiment 3

[0059] Duration of Polyinosinic Acid Administration and Risk of Bacterial Infection

[0060] Second, we observed the time point at which the bacterial clearance rate decreased in the animal body after polyinosinic acid administration. Since viral infections, such as influenza, usually last for several days or even longer, we conducted related experimental studies, taking polyinosinic acid in 1 dose or 3 doses to simulate the effect of viral infection. After 24 hours of intranasal administration of polyinosinic acid or saline once or three times, the experimental animals were intrathecally injected with Streptococcus pneumoniae. At 48h, record the amount of bacteria in the body. We found that the dose of polyinosinic acid correlated with the rate of bacterial clearance. The bacterial clearance rate in the experimental animals with one-time administration of polyinosinic acid will tend to decrease (8 times higher than the average CFU value of the normal saline control group, p...

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Abstract

The invention relates to the field of biological medicine, in particular to an application of poly inosine-cytidine, imiquimod and gardiquimod in constructing a virus immunity mouse model. The inventor of the invention employs the mouse model and forms an antivirus immune state by using poly inosine-cytidine, imiquimod and gardiquimod; an experiment mouse administered with poly inosine-cytidine is found to appear lung bacterium clearance impairment; in addition, poly inosine-cytidine is found to be capable of mediating IFNI expression; and finally, IFNI can induce a defense mechanism of a lung against gram positive pathogenic bacteria.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to the use of polyinosinic acid, imiquimod and gademot in constructing virus immune mouse models. Background technique [0002] Respiratory viral infections are common and often exhibit a benign clinical course. However, a significant proportion of patients develop concomitant or secondary bacterial infection, a complication that can lead to respiratory failure or death. Although outbreaks of such complications are highest in children, the elderly, and immunosuppressed populations, viral bacterial pneumonia can also occur in healthy adults and result in a significant disease burden. Viral-bacterial pneumonia has been repeatedly reported following the prevalence of influenza infection. It was the leading cause of death in patients during the influenza epidemics of the 20th century and the 2009 H1N1 influenza pandemic. [0003] The mechanisms by which viral infection contributes to bacte...

Claims

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Application Information

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IPC IPC(8): A61K31/713A61K31/4745A61P31/12A61P31/04A61P11/00C12Q1/06
CPCA61K31/713A61K31/4745C12Q1/06
Inventor 田晓丽
Owner 宁波美丽人生医药生物科技发展有限公司
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