title: CpG-DNA protects against a lethal orthopoxvirus infection in a murine model.
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.
authors.affiliation: Defence Science and Technology Laboratory (DSTL), Porton Down, Salisbury, Wiltshire SP4 0JQ, UK. crees1@dstl.gov.uk
authors.forename: D G Cerys
authors.initials: DG
authors.lastname: Rees
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Gates
authors.forename: Michael
authors.initials: M
authors.lastname: Green
authors.forename: Lin
authors.initials: L
authors.lastname: Eastaugh
authors.forename: Roman A
authors.initials: RA
authors.lastname: Lukaszewski
authors.forename: Kate F
authors.initials: KF
authors.lastname: Griffin
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Krieg
authors.forename: Richard W
authors.initials: RW
authors.lastname: Titball
mesh_terms: D000818:Animals; D001483:Base Sequence; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000494:pharmacology*; D011213:Poxviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D014616:Vaccinia virus / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects
chemical_list: C408982:CPG-oligonucleotide; D018925:Chemokines; D016207:Cytokines; D009838:Oligodeoxyribonucleotides