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Published on: May 24, 2020
CpG-DNA protects against a lethal orthopoxvirus infection in a murine model
D G Cerys Rees1, Amanda J Gates, Michael Green
1Defence Science and Technology Laboratory (DSTL), Porton Down, Salisbury, Wiltshire SP4 0JQ, UK. crees1@dstl.gov.uk
Abstract:
CpG-DNA has been described as a potent activator of the innate immune system, with potential to protect against infection caused by a range of pathogens in a non-specific manner. Here two classes of CpG-DNA (CpG-A and CpG-B) have been investigated for their abilities to protect mice from infection with an orthopoxvirus (vaccinia virus). Dosing with either CpG-A or B by the intraperitonal or intranasal route protected mice against a subsequent intranasal challenge with vaccinia virus. To our knowledge, this is the first time CpG-mediated protection has been demonstrated at the lung surface. The level of protection was greater when CpG-DNA was administered intranasally demonstrating a clear relationship between the route of CpG dosing and infection route. Treatment with CpG-B reduced viral titer in the lung by 10,000-fold at day 3 post-infection. The CC chemokines RANTES and MIP-1beta were elevated in the broncho-alveolar lavage from animals treated intranasally with CpG-B compared to untreated and intraperitoneally dosed controls, and it is possible that these chemokines play a role in the clearance of intranasally delivered vaccinia virus.
Insights
CpG-DNA administration protected mice against vaccinia virus infection, especially when delivered intranasally to the lung surface. This CpG-DNA immunotherapy shows promise for treating viral respiratory infections.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- CpG-DNA activates the innate immune system, offering broad protection against pathogens.
- Orthopoxviruses, like vaccinia virus, pose significant health risks.
Purpose of the Study:
- To investigate the efficacy of two CpG-DNA classes (CpG-A and CpG-B) in protecting mice against vaccinia virus infection.
- To determine the optimal route of CpG-DNA administration for protection against respiratory viral challenge.
Main Methods:
- Mice were treated with CpG-A or CpG-B via intraperitoneal or intranasal routes.
- Mice were subsequently challenged intranasally with vaccinia virus.
- Viral titers in the lungs and chemokine levels in broncho-alveolar lavage were analyzed.
Main Results:
- Both CpG-A and CpG-B provided protection against intranasal vaccinia virus challenge.
- Intranasal administration of CpG-DNA demonstrated superior protection compared to intraperitoneal dosing.
- CpG-B treatment significantly reduced lung viral titers (10,000-fold) and elevated key chemokines (RANTES, MIP-1beta).
Conclusions:
- CpG-DNA immunotherapy can protect against orthopoxvirus infection at the lung surface, a novel finding.
- Intranasal delivery of CpG-DNA is an effective strategy for enhancing protection against respiratory viral infections.
- Elevated CC chemokines may contribute to CpG-DNA-mediated viral clearance in the lungs.
