orabase and Virus-Diseases

The International Consortium on Anti-Virals (ICAV) is a nonprofit organization that aims to support the development of antivirals for life-threatening and emerging viruses. In recent years, ICAV's emphasis has been predominantly on tropical viruses and avian influenza. The Sixth International Symposium of the ICAV was held at Trent University, Peterborough, Canada, and at MaRs Discovery District, Toronto, Canada, 4-6 May 2008. Approximately 100 participants representing 12 countries attended the symposium. This meeting report focuses on two thought-provoking presentations on topics that require immediate attention: the development of potent broad-spectrum antivirals against emerging viruses and the assessment of the risk of a H5N1 influenza pandemic.

Topics: Animals; Antiviral Agents; Carboxymethylcellulose Sodium; Chickens; Communicable Diseases, Emerging; Disease Outbreaks; Humans; Influenza A Virus, H5N1 Subtype; Influenza in Birds; Influenza, Human; Liposomes; Mice; Peptides; Poultry Diseases; Risk; Virus Diseases; Viruses

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.

Topics: Animals; Carboxymethylcellulose Sodium; CpG Islands; Encephalitis Virus, Western Equine; Encephalomyelitis, Equine; Humans; Influenza A virus; Influenza, Human; Liposomes; Mice; Oligodeoxyribonucleotides; Poly I-C; Polylysine; Respiratory Tract Infections; Virus Diseases

Fourteen patients with severe viral illnesses were given intravenous infusions of a modified interferon inducer, polyriboinosinic-polyribocytidylic acid-poly-L-lysine complexed with carboxymethylcellulose [poly)I:C.LC)], during a phase 1 clinical trial. The first eight patients received 0.15 to 0.30 mg of poly(I:C.LC) per kg of body weight daily for 5 consecutive days, and another received two courses separated by 1 week. A second group of five patients was given single intravenous infusions of 0.10 to 0.15 mg of poly(I:C.LC) per kg. Interferon was detectable in the serum 8 to 16 h after injection. Titers ranged from 15 to 800 U/ml and varied directly with the dose of poly(I:C.LC). Interferonemias persisted for 12 to 48 h. In patients receiving 5-day courses of poly(I:C.LC), lower levels of serum interferon (0 to 160 U/ml) occurred on days 2 through 5, characteristic of a hyporesponsive state. An exception was a 69-year-old patient with disseminated varicella zoster, multiple myeloma, and renal insufficiency whose serum contained 3,150 U of interferon per ml on day 3 of 0.3 mg of poly(I:C.LC) per kg. Fever (39 to 40.5 degrees C, rectally; 13 of the 14 patients) peaked 3 to 8 h after completion of infusions. Other toxic effects included lymphopenia (10 of the 14 patients), hypotensive episodes (7 of the 14 patients), and minor elevations of serum glutamicoxalacetic transaminase and lactic dehydrogenase.

Topics: Adolescent; Adult; Aged; Carboxymethylcellulose Sodium; Drug Evaluation; Female; Fever; Humans; Hypotension; Interferons; Liver; Lymphopenia; Male; Poly I-C; Polylysine; Virus Diseases