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

摘要

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-y 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 pheno-type (CD62L~(10), 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.