Enhanced antigen-specific primary CD4+ and CD8+ responses by codelivery of ovalbumin and toll-like receptor ligand monophosphoryl lipid A in poly(D,L-lactic-co-glycolic acid) nanoparticles.
The purpose of this research was to investigate the use of biodegradable poly(D,L-lactic-co-glycolic acid) nanoparticles (PLGA-NP) as a vaccine delivery system to codeliver antigen, ovalbumin (OVA) along with monophosphoryl lipid A (MPLA) as adjuvant for induction of potent CD4(+) and CD8(+) T cell responses. The primary CD4(+) T responses to OVA/MPLA NP were investigated using OVA-specific T cells from DO11.10 transgenic mice. Following adoptive transfer of these cells, mice were immunized s.c. by NP formulations. For assessing the CD8(+) responses, bone marrow derived dendritic cells (DCs) were pulsed with different OVA formulations, then, cocultured with CD8(+) T cells from OT-1 mice. T cell proliferation/activation and IFN-gamma secretion profile have been examined. Particulate delivery of OVA and MPLA to the DCs lead to markedly increase in in vitro CD8(+) T cell T cell proliferative responses (stimulation index >3000) and >13-folds increase in in vivo clonal expanded CD4(+) T cells. The expanded T cells were capable of cytokine secretion and expressed an activation and memory surface phenotype (CD62L(lo), CD11a(hi), and CD44(hi)). Codelivery of antigen and MPLA in PLGA-NP offers an effective method for induction of potent antigen specific CD4(+) and CD8(+) T cell responses.
Hamdy
Samar
S
Faculty of Pharmacy and Pharmaceutical Sciences, 3133 Dentistry/Pharmacy Centre, University of Alberta, Edmonton, Alberta, Canada, T6G 2N8.
Elamanchili
Praveen
P
Alshamsan
Aws
A
Molavi
Ommoleila
O
Satou
Tadaaki
T
Samuel
John
J
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002999:Clone Cells; D016207:Cytokines / Q000378:metabolism; D000939:Epitopes / Q000187:drug effects / Q000276:immunology*; D006016:Glycolates / Q000008:administration & dosage* / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007700:Kinetics; D019344:Lactic Acid; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage*; D010047:Ovalbumin / Q000008:administration & dosage* / Q000494:pharmacology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility / Q000187:drug effects; D051193:Toll-Like Receptors / Q000276:immunology; D014611:Vaccination
D016207:Cytokines; D000939:Epitopes; D006016:Glycolates; D008050:Lipid A; D051193:Toll-Like Receptors; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D010047:Ovalbumin; C048436:monophosphoryl lipid A