Key result
Triple combination therapy of favipiravir plus anti-Stem and anti-RBS monoclonal antibodies completely eradicated influenza virus from nude mice, resulting in 100% survival at 188 days.
Why the study?
Immunocompromised influenza patients require prolonged treatment with neuraminidase inhibitors because their immune system fails to eradicate the virus, creating a need for effective virus-eradicating therapies.
Does triple combination therapy of favipiravir, anti-Stem mAb, and anti-RBS mAb improve survival and eradicate influenza virus in immunocompromised nude mice?
Does triple combination therapy of favipiravir, anti-Stem mAb, and anti-RBS mAb improve survival and eradicate influenza virus in immunocompromised nude mice?
Absolute Event Rate: 100% vs 0%
p-value: p=<0.01
Triple combination therapy of favipiravir and two monoclonal antibodies successfully eradicated influenza virus and prevented mortality in an immunocompromised mouse model.
Hypothesis-generating for triple antiviral therapy in immunocompromised hosts; clinical translation requires prospective human trials.
Prolonged treatment of immunocompromised influenza patients with viral neuraminidase (NA) inhibitors is required, because the immune system of such patients fails to eradicate the viruses. Here, we attempted to eradicate influenza virus from the respiratory organs of nude mice, which is a model of immunocompromised hosts, by using combination therapy of the viral polymerase inhibitor favipiravir and monoclonal antibodies (mAbs) against the receptor-binding site (RBS) and stem of viral hemagglutinin (HA). Although monotherapy or combination therapy of two antivirals (two mAbs or favipiravir plus a mAb) suppressed virus replication, they failed to eradicate viruses from nude mice. In contrast, the triple combination therapy of favipiravir plus anti-Stem and anti-RBS mAbs completely stopped virus replication in nude mice, resulting in virus clearance. Triple combination approaches should be considered for the treatment of human immunocompromised patients with severe influenza.
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Kiso et al. (2020) studied Influenza virus infection (immunocompromised model) (n=105). Favipiravir plus anti-Stem and anti-RBS monoclonal antibodies vs. Methyl cellulose plus PBS (vehicle control), monotherapies, and dual therapies was evaluated on Survival at 188 days (p=<0.01). Triple combination therapy of favipiravir plus anti-Stem and anti-RBS monoclonal antibodies completely eradicated influenza virus from nude mice, resulting in 100% survival at 188 days.
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