Background Influenza A viruses can replicate in the olfactory mucosa and subsequently use the olfactory nerve to enter the central nervous system (CNS). It is currently unknown whether intervention strategies are able to reduce or prevent influenza virus replication within the olfactory mucosa and subsequent spread to the CNS. Therefore, we tested the efficacy of homologous vaccination and prophylactic oseltamivir to prevent H5N1 virus CNS invasion via the olfactory nerve in our ferret model.
Methods Ferrets were vaccinated intramuscularly or received oseltamivir (5 mg/kg twice daily) prophylactically before intranasal inoculation of highly pathogenic H5N1 virus (A/Indonesia/05/2005) and were examined using virology and pathology.
Results Homologous vaccination reduced H5N1 virus replication in the olfactory mucosa and prevented subsequent virus spread to the CNS. However, prophylactic oseltamivir did not prevent H5N1 virus replication in the olfactory mucosa sufficiently, resulting in CNS invasion via the olfactory nerve causing a severe meningoencephalitis.
Conclusions Within our ferret model, vaccination is more effective than prophylactic oseltamivir in preventing CNS invasion by H5N1 virus via the olfactory nerve. This study highlights the importance of including the olfactory mucosa, olfactory nerve, and CNS tissues in future vaccine and antiviral studies, especially for viruses with a known neurotropic potential.

Additional Metadata
Keywords Encephalitis, Ferret, H5N1, Influenza, Olfactory mucosa, Olfactory nerve, Oseltamivir, Vaccine, Virus
Persistent URL dx.doi.org/10.1093/infdis/jiw123, hdl.handle.net/1765/125713
Journal The Journal of Infectious Diseases
Citation
Siegers, J.Y, van den Brand, J.M.A, Leijten, L.M.E, van de Bildt, M.W.G, van Run, P.R.W.A, van Amerongen, G, … van Riel, D.A.J. (2016). Vaccination is more effective than prophylactic oseltamivir in preventing cns invasion by h5n1 virus via the olfactory nerve. The Journal of Infectious Diseases, 214(4), 516–524. doi:10.1093/infdis/jiw123