Pre-Exposure Intranasal Treatment with Neomycin Sulfate Reduces Transmission of Influenza B Virus

<b>Background/Objectives</b>: Influenza B virus infection contributes substantially to annual morbidity and mortality, accounting for 20% to 30% of influenza-associated deaths worldwide. Although vaccination reduces the risk of severe disease, widely used inactivated influenza vaccines are often insufficient to prevent virus transmission. Moreover, influenza B viruses are less susceptible to commonly used antivirals than influenza A viruses. New approaches are therefore required to decrease disease burden and limit virus spread. Neomycin, an aminoglycoside antibiotic, was recently shown to mitigate SARS-CoV-2 transmission in a hamster model. Here, we conducted an exploratory study to assess the effect of neomycin on influenza B virus transmission. <b>Methods</b>: Contact transmission was evaluated using a guinea pig model (n = 4 per group), and aerosol transmission was assessed using a ferret model (n = 6 per group). Animals in the experimental groups received neomycin sulfate (5 mg/guinea pig, 20 mg/ferret) or placebo intranasally, starting one day before exposure to infected animals and continuing for four days thereafter. In the guinea pig study, an additional control group received intranasal interferon alpha. Viral transmission to contact animals was assessed by RT-PCR and virus culture of nasal washes collected over two weeks. Clinical signs and body weight were monitored daily. <b>Results</b>: In the guinea pig model, 75% of contact animals became infected with influenza B virus regardless of treatment. Neither neomycin nor interferon alpha prevented infection, although both delayed the onset of viral shedding in contact animals. In the ferret model, infection occurred in 33% of placebo-treated contact animals, whereas no viral shedding was detected in the neomycin-treated group. <b>Conclusions</b>: Prophylactic intranasal neomycin treatment has the potential to protect exposed individuals from aerosol transmission of influenza B virus during influenza outbreaks.