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‐γ 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. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res 80A:, 2007