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

Wilson, K, Xiang, S and 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', Frontiers in Microbiology, vol. 6, 29, pp. 1-9.


Document type: Journal Article
Collection: Journal Articles

Title 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
Author(s) Wilson, K
Xiang, S
Plebanski, M
Year 2015
Journal name Frontiers in Microbiology
Volume number 6
Article Number 29
Start page 1
End page 9
Total pages 9
Publisher Frontiers Research Foundation
Abstract The development of practical and flexible vaccines to target liver stage malaria parasites would benefit from an ability to induce high levels of CD8 T cells to minimal peptide epitopes. Herein we compare different adjuvant and carrier systems in a murine model for induction of interferon gamma (IFN-γ) producing CD8 T cells to the minimal immuno-dominant peptide epitope from the circumsporozoite protein (CSP) of Plasmodium berghei, pb9 (SYIPSAEKI, referred to as KI). Two pro-inflammatory adjuvants, Montanide and Poly I:C, and a non-classical, non-inflammatory nanoparticle based carrier (polystyrene nanoparticles, PSNPs), were compared side-by-side for their ability to induce potentially protective CD8 T cell responses after two immunizations. KI in Montanide (Montanide + KI) or covalently conjugated to PSNPs (PSNPs-KI) induced such high responses, whereas adjuvanting with Poly I:C or PSNPs without conjugation was ineffective. This result was consistent with an observed induction of an immunosuppressed environment by Poly I:C in the draining lymph node (dLN) 48 h post injection, which was reflected by increased frequencies of myeloid derived suppressor cells (MDSCs) and a proportion of inflammation reactive regulatory T cells (Treg) expressing the tumor necrosis factor receptor 2 (TNFR2), as well as decreased dendritic cell (DC) maturation. The other inflammatory adjuvant, Montanide, also promoted proportional increases in the TNFR2+ Treg subpopulation, but not MDSCs, in the dLN. By contrast, injection with non-inflammatory PSNPs did not cause these changes. Induction of high CD8 T cell responses, using minimal peptide epitopes, can be achieved by non-inflammatory carrier nanoparticles, which in contrast to some conventional inflammatory adjuvants, do not expand either MDSCs or inflammation reactive Tregs at the site of priming
Subject Immunology not elsewhere classified
Keyword(s) Adjuvant
CD8 peptide
Malaria
MDSC
Nanoparticle
Treg
DOI - identifier 10.3389/fmicb.2015.00029
Copyright notice © 2015 Wilson, Xiang and Plebanski.
ISSN 1664-302X
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