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Synthetic mast-cell granules as adjuvants to promote and polarize immunity in lymph nodes


Granules of mast cells (MCs) enhance adaptive immunity when, on activation, they are released as stable particles. Here we show that submicrometre particles modelled after MC granules augment immunity when used as adjuvants in vaccines. The synthetic particles, which consist of a carbohydrate backbone with encapsulated inflammatory mediators such as tumour necrosis factor, replicate attributes of MCs in vivo including the targeting of draining lymph nodes and the timed release of the encapsulated mediators. When used as an adjuvant during vaccination of mice with haemagglutinin from the influenza virus, the particles enhanced adaptive immune responses and increased survival of mice on lethal challenge. Furthermore, differential loading of the particles with the cytokine IL-12 directed the character of the response towards Th1 lymphocytes. The synthetic MC adjuvants replicate and enhance the functions of MCs during vaccination, and can be extended to polarize the resulting immunity.

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Figure 1: Synthetic particles are modelled after MC-derived particles.
Figure 2: Physical characteristics of synthetic particles, and mediator encapsulation.
Figure 3: Synthetic particles flow freely to the draining LN.
Figure 4: Particulate TNF as an adjuvant promotes germinal-centre production.
Figure 5: Particulate TNF is an effective adjuvant that protects against a lethal flu challenge.
Figure 6: Differential particle loading with IL-12 promotes Th1 polarized immunity.


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We thank C. A. Kunder, B. Berwin and A. Alonso for their contributions to producing the image in Fig. 1a. L. Eibist is thanked for her assistance in acquiring the EM of synthetic particles. We also thank A. P. S. Rathore and W. X. G. Ang for their manuscript review and discussions. The authors’ work is supported by the US National Institutes of Health grants R01 AI96305, R01 AI35678, R01 DK077159, R01 AI50021, R37 DK50814 and R21 AI056101.

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Experiments were designed by A.L.S. and S.N.A., with H.F.S. contributing to the experimental design of vaccination studies and K.W.L. contributing to the experimental design of studies relating to particle synthesis and characterization. Experiments were carried out by A.L.S. and C.Y.C. Data was analysed by A.L.S. and C.Y.C. with advice from S.N.A. and H.F.S. The manuscript was written primarily by A.L.S. All authors contributed to discussions and manuscript review.

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Correspondence to Ashley L. St. John.

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St. John, A., Chan, C., Staats, H. et al. Synthetic mast-cell granules as adjuvants to promote and polarize immunity in lymph nodes. Nature Mater 11, 250–257 (2012).

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