TLR ligands and antigen need to be coencapsulated into the same biodegradable microsphere for the generation of potent cytotoxic T lymphocyte responses.
Dendritic cells phagocytose pathogens leading to maturation and cross-presentation on MHC class I. We found that the efficiency of cross-priming in mice after vaccination with biodegradable poly(D,L-lactide-co-glycolide) microspheres (MSs) was enhanced when ovalbumin was coencapsulated together with either a CpG oligonucleotide or polyI:C as compared to co-inoculation of ovalbumin-bearing MS with soluble or separately encapsulated adjuvants. A single immunization with MS containing coencaspsulated CpG and ovalbumin yielded 9% SIINFEKL/H-2K(b) tetramer positive CTLs, production of IFN-gamma, efficient cytolysis, and protection from vaccinia virus infection. Taken together, coencapsulation of adjuvant and antigen is an important paradigm for the generation of potent CTL responses.
Schlosser
Eva
E
Division of Immunology, Department of Biology, Konstanz, Germany.
Mueller
Marc
M
Fischer
Stefan
S
Basta
Sameh
S
Busch
Dirk H
DH
Gander
Bruno
B
Groettrup
Marcus
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000941:Antigens / Q000008:administration & dosage*; D001854:Bone Marrow Cells / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D018899:CpG Islands; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D004339:Drug Compounding; D005079:Excipients; D005434:Flow Cytometry; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology*; D007369:Interferon Inducers / Q000494:pharmacology; D019344:Lactic Acid; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D018995:Myosin Heavy Chains / Q000378:metabolism; D009841:Oligonucleotides / Q000494:pharmacology; D011070:Poly I-C; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D051193:Toll-Like Receptors / Q000187:drug effects*
D000276:Adjuvants, Immunologic; D000941:Antigens; D016207:Cytokines; D005079:Excipients; D007369:Interferon Inducers; D008024:Ligands; D009841:Oligonucleotides; D051193:Toll-Like Receptors; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D018995:Myosin Heavy Chains; D011070:Poly I-C