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
✍ Scribed by Samar Hamdy; Praveen Elamanchili; Aws Alshamsan; Ommoleila Molavi; Tadaaki Satou; John Samuel
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 609 KB
- Volume
- 81A
- Category
- Article
- ISSN
- 1549-3296
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✦ Synopsis
Abstract
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