Prophylaxis of acute respiratory virus infections using nucleic acid-based drugs.
Acute respiratory virus infections such as SARS and pandemic influenza are highly contagious diseases that cause global crisis, and inflict severe human mortality and morbidity. Vaccines against these viruses are either unavailable or do not provide adequate protection. In the absence of effective vaccines, nucleic acid-based immunomodulators have the potential to offer effective, broad-spectrum protection against these deadly pathogens. Poly ICLC and CpG oligonucleotides are promising gene-based drugs which have been shown in animal studies to protect against acute respiratory virus infections. Poly ICLC is a synthetic double-stranded RNA (dsRNA), and an effective interferon-inducer and natural killer cell activator. When encapsulated in liposomes, poly ICLC offers complete protection (100% survival rate in pretreated group versus 0% survival in control group) against a lethal respiratory challenge of influenza A virus in mice. This antiviral effect has been shown to persist for up to 3 weeks post-drug treatment. Poly ICLC pretreatment also protects mice against a respiratory challenge of western equine encephalitis (WEE) virus, at a level comparable to inactivated WEE vaccine. CpG oligos in liposomes also provided high level of protection against the lethal influenza challenge. Together, these studies suggest nucleic acid-based immunomodulators are promising antiviral agents which can offer effective and non-specific protection against acute respiratory virus infections.
Wong
Jonathan P
JP
Defence R&D Canada--Suffield, Alberta, Canada. jonathan.wong@drdc-rddc.gc.ca
Nagata
Les P
LP
Christopher
Mary E
ME
Salazar
Andres M
AM
Dale
Roderic M K
RM
D000818:Animals; D002266:Carboxymethylcellulose Sodium / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D018899:CpG Islands; D004667:Encephalitis Virus, Western Equine; D004683:Encephalomyelitis, Equine / Q000517:prevention & control; D006801:Humans; D009980:Influenza A virus; D007251:Influenza, Human / Q000517:prevention & control; D008081:Liposomes; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000494:pharmacology*; D011070:Poly I-C / Q000008:administration & dosage / Q000494:pharmacology*; D011107:Polylysine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012141:Respiratory Tract Infections / Q000517:prevention & control*; D014777:Virus Diseases / Q000517:prevention & control*
C408982:CPG-oligonucleotide; D008081:Liposomes; D009838:Oligodeoxyribonucleotides; D011107:Polylysine; C019531:poly ICLC; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C