Induction of a CD8+ cytotoxic T lymphocyte response to soluble antigen given together with a novel muramyl dipeptide adjuvant, N-acetyl-D-glucosaminyl-(beta 1-4)-N-acetylmuramyl-L-alanyl-D-isoglutamine (GMDP).
We have investigated the ability of the novel muramyl dipeptide, GMDP, to act as an adjuvant for the induction of ovalbumin (OVA)-specific, CD8+ cytotoxic T lymphocyte (CTL) responses. C57Bl/6 mice were twice immunized s.c. with 50 micrograms OVA emulsified with a squalane, L121 pluronic containing Tween-80 vehicle either with (STP-GMDP) or without (STP) GMDP. Splenic precursor CD8+ CTL activity against E.G7-OVA, but not against EL-4 parental targets was detected in STP-GMDP immunized mice after 5 days of in vitro re-stimulation with irradiated E.G7-OVA cells, while mice immunized with OVA in STP alone or OVA alone failed to demonstrate CTL activity. OVA emulsified in a microfluidized STP vehicle formulation without GMDP also elicited the E.G7-OVA precursor CTL. The ability of GMDP to induce a class I-restricted, CD8+ CTL response to a soluble protein antigen may have implications for the development of useful vaccines against viral pathogens or tumours against which CTL responses are desirable.
Hornung
R L
RL
Biological Carcinogenesis & Development Program, Program Resources, Inc./DynCorp, Frederick, MD, USA.
Longo
D L
DL
Gowda
V L
VL
Kwak
L W
LW
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D007114:Immunization; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D012995:Solubility; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D000941:Antigens; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C023868:N-acetyl-beta-glucosaminyl-N-acetylmuramyl-alanylisoglutamine; D010047:Ovalbumin