The relationship between nanoparticles and immunity: the ups and the downs
Magdalena Plebanski*
Department of Immunology and Pathology, Alfred Hospital Precinct
and
Division of Therapeutics and Regenerative Medicine, Monash Institute of Medical Engineering (MIME)
Monash University, Melbourne, Australia
Nanoparticles used for in vivo drug delivery, diagnostics or vaccine carriers require vastly different modes of interaction with the immune system, to perform their functionoptimally. Thus, drug delivery and diagnostics require stealth properties, to prevent non-specific elimination from the body by the immune system, whilst targeted delivery can be enabled by decorating their surface with cell specific targeting ligands. Nanoparticles used as vaccine carriers by contrast aim to be highly visible to the immune system and often target antigen presenting cells (APC) such as dendritic cells (DC), and may additionally show adjuvant properties, usually by causing DC activation by themselves, or via the incorporation of conventional adjuvants such as toll like receptor (TLR) ligand agonists. In this presentation we will share key insights from our >20 years of research in this field1-2, as well as our recent studies3-5, and showcase how minute changes in size, charge, shape and material dramatically change how activating immune cells such as macrophages and DC, as well as suppressor immune cells,such as myeloid derived suppressor cells (MDSC) and regulatory T cells (Tregs) react to such nanoparticles. We will also discuss recent collaborative studies using nanoparticles further surface modified with either inert (pullulan-unpublished) or immunostimulatory carbohydrates (mannan or hyaluronan)4-5and their differential potential in the development of novel vaccines. We will also evaluate the controversial new area of non-specific or heterologous effects of vaccines, and how it will impact the development of synthetic nanoparticle based vaccines6.
References
1 . Fifis T, Gamvrellis A, Crimeen-Irwin B, Pietersz GA, Li J, Mottram PL, McKenzie IF, Plebanski M Size-dependent immunogenicity: therapeutic and protective properties of nano-vaccines against tumors. J Immunol. 2004 173(5):3148-54
2. Nawwab Al-Deen F, Ma C, Xiang SD, Selomulya C, Plebanski M*, Coppel RL* (2013)On the efficacy of malaria DNA vaccination with magnetic gene vectors.J Control Release168(1):10-7
3. Wilson KL, Xiang SD, Plebanski M. (2015) Montanide, Poly I:C and nanoparticle based vaccines promote differential suppressor and effector cell expansion: a study of induction of CD8 T cells to a minimal Plasmodium berghei epitope Front Microbiol. 6:29.
4. Al-Deen FM, Xiang SD, Ma C, Wilson K, Coppel RL, Selomulya C*, Plebanski M*(2017) Magnetic Nanovectors for the Development of DNA Blood-Stage Malaria Vaccines. Nanomaterials (Basel) 7(2). pii: E30
5. Kempe K, Xiang SD, Wilson P, Rahim MA, Ju Y, Whittaker MR, Haddleton DM, Plebanski M*, Caruso F*, Davis TP*. (2017) Engineered Hydrogen-Bonded Glycopolymer Capsules and Their Interactions with Antigen Presenting Cells. ACS Appl Mater Interfaces.9(7):6444-6452 (*equal contribution)
6. Fish EN, Flanagan KL,.. Netea MG, Plebanski M, Rowland-Jones SL, Selin LK, Shann F, Whittle HC (2016) Changing oral vaccine to inactivated polio vaccine might increase mortality. Lancet.387(10023):1054-5