The induction of virus-neutralizing antibodies in influenza A-infected mice treated with Oseltamivir phosphate: effect of dosage and scheduling.

Abstract

Oseltamivir phosphate (OS) is currently the most frequently used influenza antiviral drug. It moderates the course of influenza virus type A (IAV) infection, however, its impact on the induction of virus-neutralizing antibodies (VNAbs) is not understood in details. Here, we examined the influence of low (10 mg/kg) or high (60 mg/kg) doses of OS on the viral titer in lungs of BALB/c mice infected with 0.5 LD50 of IAV and on the level of VNAbs. Prophylactic application of OS (6 h before the infection) delayed the increase of viral titer in lungs with a lower peak in comparison to non-treated control mice. After therapeutic OS application (44 h after the infection), maximum of virus titer did not significantly change. However, the induction of VNAbs strongly decreased, to 16.7%-18.1% of the control, after preventive application of high OS dose. A minimal decrease of VNAbs titers was observed in groups of mice treated with low dose of OS applied therapeutically. They lowered to 91.1% / 14 or to 94.1% / 21 days post infection (p.i.) of VNAbs titers of non-treated control mice. In all other groups, levels of VNAbs titers dropped to 26.5-53.7% of those of non-treated mice. It should be noted that VNAbs titers were in direct proportion to maximal virus titers in mouse lungs of corresponding groups. In summary, after OS application the clinical symptoms of the disease were milder or non-observable in all OS-treated groups, but the lowering of VNAbs titers was dependent on the OS dose and interval between drug app-lication and the start of infection. Keywords: influenza A virus; Oseltamivir; prophylactic treatment; therapeutic treatment; virus-neutralizing antibodies.