Effect of MDP-Lys(L18) as a mucosal immunoadjuvant on protection of mucosal infections by Sendai virus and rotavirus.
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 using suckling mice (10-day-old) inoculated perorally (p.o.) with 1.5 x 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 micrograms 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 micrograms mouse-1) or intranasally (i.n., 100 micrograms mouse-1) various days before Sendai virus infection (2.6 x 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.
Fukushima
A
A
Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Yoo
Y C
YC
Yoshimatsu
K
K
Matsuzawa
K
K
Tamura
M
M
Tono-oka
S
S
Taniguchi
K
K
Urasawa
S
S
Arikawa
J
J
Azuma
I
I
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000281:Administration, Intranasal; D000284:Administration, Oral; D000285:Administration, Rectal; D000818:Animals; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000276:immunology / Q000821:virology; D011247:Pregnancy; D018108:Respirovirus / Q000187:drug effects / Q000254:growth & development / Q000276:immunology; D010253:Respirovirus Infections / Q000517:prevention & control*; D012401:Rotavirus / Q000187:drug effects / Q000254:growth & development / Q000276:immunology; D012400:Rotavirus Infections / Q000517:prevention & control*; D017186:Titrimetry
D000276:Adjuvants, Immunologic; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C036866:romurtide