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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 KL, Xiang SD, Plebanski M - Front Microbiol (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC Australia.

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.

No MeSH data available.


Related in: MedlinePlus

Size distribution for PSNPs-KI formulations. SYIPSAEKI peptides were covalently conjugated to PSNPs, and the final sizes were measured by dynamic light scattering instruments (Zetasizer).
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Figure 1: Size distribution for PSNPs-KI formulations. SYIPSAEKI peptides were covalently conjugated to PSNPs, and the final sizes were measured by dynamic light scattering instruments (Zetasizer).

Mentions: Peptide delivery by nanoparticles (either mixed or conjugated) was compared for immunogenicity in vivo using BALB/c mice. To generate the conjugated nanovaccine, the immune-dominant CD8 T cell peptide epitope of the CSP protein, SYIPSAEKI (KI), from P. berghei was covalently attached to carboxylated polystyrene nanoparticles (PSNPs, 40–50 nm) using an optimized covalent conjugation protocol as previously described (Xiang et al., 2013). As shown in Table 1, the average size of the PSNPs-KI formulation was 47.97 ± 2.64 nm, and the polydispersity index (PdI) was very low (0.07 ± 0.03), indicating the successful formulation of a uniformly dispersed nanoparticle formulation with a narrow size distribution range (Figure 1). The antigen loading was 0.32 ± 0.09 mg/ml, which represented 1032.6 ± 147.8 peptide molecules per particle (Table 1). The number of peptide molecules per particle was comparable to previous studies with a model peptide antigen, SIINFEKL, where potent responses were observed at that loading (Xiang et al., 2013).


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 KL, Xiang SD, Plebanski M - Front Microbiol (2015)

Size distribution for PSNPs-KI formulations. SYIPSAEKI peptides were covalently conjugated to PSNPs, and the final sizes were measured by dynamic light scattering instruments (Zetasizer).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4319470&req=5

Figure 1: Size distribution for PSNPs-KI formulations. SYIPSAEKI peptides were covalently conjugated to PSNPs, and the final sizes were measured by dynamic light scattering instruments (Zetasizer).
Mentions: Peptide delivery by nanoparticles (either mixed or conjugated) was compared for immunogenicity in vivo using BALB/c mice. To generate the conjugated nanovaccine, the immune-dominant CD8 T cell peptide epitope of the CSP protein, SYIPSAEKI (KI), from P. berghei was covalently attached to carboxylated polystyrene nanoparticles (PSNPs, 40–50 nm) using an optimized covalent conjugation protocol as previously described (Xiang et al., 2013). As shown in Table 1, the average size of the PSNPs-KI formulation was 47.97 ± 2.64 nm, and the polydispersity index (PdI) was very low (0.07 ± 0.03), indicating the successful formulation of a uniformly dispersed nanoparticle formulation with a narrow size distribution range (Figure 1). The antigen loading was 0.32 ± 0.09 mg/ml, which represented 1032.6 ± 147.8 peptide molecules per particle (Table 1). The number of peptide molecules per particle was comparable to previous studies with a model peptide antigen, SIINFEKL, where potent responses were observed at that loading (Xiang et al., 2013).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC Australia.

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.

No MeSH data available.


Related in: MedlinePlus