Rigging Innate Immunity against the Flu

• Published in: Molecular therapy Vol. 25; no. 9; pp. 1993 - 1994
• Main Author: Krieg, Arthur M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.09.2017; Elsevier Limited; American Society of Gene & Cell Therapy
• Subjects: Clinical trials; Diagnosis; Double-stranded RNA; Geriatrics; Immune response; Infections; Influenza; Ligands; Pandemics; Pathogens; Pneumonia; Population studies; Prophylaxis; Studies
• ISSN: 1525-0016; 1525-0024; 1525-0024
• DOI: 10.1016/j.ymthe.2017.08.008

Main Text In addition to providing great material for Hollywood movies, infectious pandemics pose a real threat to mankind. [...]the development of novel prophylactic and therapeutic approaches is a high priority. In routine clinical practice, therapeutic administration within 30 hr of infection is likely to be challenging and may be impractical considering the time required to make a diagnosis, but it is possible to envision postexposure therapy in specific settings.7 RIG-I does not detect viruses that lack a 5′ triphosphate or diphosphate in a blunt-ended double-stranded RNA, but triggering RIG-I with a synthetic ligand may, nevertheless, protect against pathogens that otherwise would not trigger this pathway during infection. Question Comment Is the treatment safe in healthy subjects? large clinical trials are likely to be required to demonstrate safety Could treatment increase the risk of other infections? activation of innate immunity can be subverted by some pathogens to improve their replication efficiency Is the treatment effective in the at-risk populations? clinical studies in pediatric and elderly populations may be required Is the route of administration practical? subcutaneous or inhaled dosing may be acceptable; i.v. is not Will the treatment cause the same or similar symptoms as infection? in a real world setting of protecting against a pandemic, the ideal treatment should not induce flu-like symptoms, as this would complicate the task of distinguishing infected from uninfected subjects Will the treatment induce a gene signature of infection? this could complicate rapid diagnosis to distinguish infected from uninfected subjects, which would be critical in a pandemic Table 1 Considerations in the Development of Innate Immune Activation as a Prophylaxis against Infection