Effect of MDP-Lys(L18) as a mucosal immunoadjuvant on protection of mucosal infections by Sendai virus and rotavirus

Abstract

To examine the effect of MDP-Lys(L18), a derivative of muramyl dipeptide (MDP), as a mucosal immunoadjuvant, we investigated its activity to augment host resistance against mucosal infections by Sendai virus and rotavirus in mice. In an experimental infection model that suckling mice (10-day-old) were inoculated perorally (p.o.) with 1.5 × 10 6 p.f.u. mouse −1 of rotavirus strain SA11, intrarectal (i.r.) as well as p.o. administration of MDP-Lys(L18) (50 μg mouse −1 prior to virus infection markedly reduced rotavirus-induced diarrhea. Furthermore, when MDP-Lys(L18) was administered p.o. (1 mg mouse −1), i.r. (300 μg mouse −1) or intranasally (i.n., 100 μg mouse −1) various days before Sendai virus infection (2.6 × 10 4 HAD mouse −1), all the mucosal administration of MDP-Lys(L18) significantly protected a lethal infection of Sendai virus, showing a dose-dependent manner. However, the efficacy of MDP-Lys(L18) to induce the prophylactic activity against the viruses somewhat varied according to the administration route and timing. In time course analysis of virus isolation in vivo, the mice administered with MDP-Lys(L18) exhibited a significant reduction of both viruses in the lungs for Sendai virus and in the bowels for rotavirus. These results suggest that MDP-Lys(L18) is a potent mucosal immunoadjuvant to enhance nonspecific host resistance against two mucosal infectious viruses, Sendai virus and rotavirus.