Low‐dose oral interferon alpha as prophylaxis against viral respiratory illness: a double‐blind, parallel controlled trial during an influenza pandemic year

Abstract

Background and objectiveInterferon alpha (IFNα) is a known antiviral agent. A double‐blind, placebo‐controlled clinical trial was conducted investigating the use of low‐dose oral interferon alpha for preventing acute viral respiratory illnesses.MethodsTwo hundred healthy adults aged 18–75 years were enrolled and completed weekly health data questionnaires to monitor for symptoms and impact of respiratory illness. Serum samples were tested for antibodies against influenza and other common respiratory viruses.ResultsLow‐dose oral IFNα prophylaxis did not reduce the incidence or impact of acute respiratory illness (ARI) or the impact of illness on daily activities. Post hoc analysis of participant subgroups, however, identified significant reductions in the incidence of ARI reported by males, those aged 50 years or more and those who received the 2009 seasonal influenza vaccine. Interferon alpha prophylaxis had a significant impact on the reporting of moderate‐to‐severe feverishness by the study population. Seropositive participants in the IFN group were more likely to report asymptomatic or mild symptoms compared with those in the placebo group who were more likely to report stronger symptoms.ConclusionsLow‐dose oral IFNα prophylaxis was not effective in limiting the overall incidence of ARI in our study population. However, there was evidence that prophylaxis reduced the severity of symptoms and had a beneficial effect in some subpopulations, including those who received the 2009 seasonal trivalent influenza vaccination.

Randomized, double-blind, placebo-controlled clinical trial to assess the safety and effectiveness of a novel dual-action oral topical formulation against upper respiratory infections

“…O'Neil et al [47] compared the efficacy of commercially available Echinacea capsules in preventing URIs symptoms compared to placebo over a period of 8 weeks during the winter months, and reported that Echinacea capsules did not significantly alter the frequency of URIs symptoms. Bennett et al [48] determined the efficacy of low dose interferon alpha (IFNα) lozenges in the prevention of URIs in healthy adults (n = 275, aged 18-75 years), based on weekly health data questionnaires. These investigators reported that lowdose oral IFN-α prophylaxis did not affect the incidence of URI, but did reduce the severity and duration of symptoms.…”

The dual role of innate immunity during influenza

“…When given prophylactically, type I IFN reduces IAV replication and disease severity in both animals [52] and humans [53] . Therapeutic administration, however, is ineffective in animal models and may actually increase lethality despite a reduction in lung IAV titers [52] .…”

Passive Broad-Spectrum Influenza Immunoprophylaxis

“…Importantly, exogenous IFN cannot be immunogenic; otherwise neutralizing antibody responses develop, rendering treatment ineffective [ 47 ]. In an attempt to overcome adverse side effects with current modes of IFN-α treatment, a recent clinical trial investigating administration of low-dose oral IFN-α prophylaxis was undertaken but was deemed ineffective in protection against acute respiratory illness during the 2009 influenza pandemic [ 48 ].…”