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

Nature Materials volume 11, pages 250–257 (2012)Cite this article

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Abstract

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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Acknowledgements

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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Author notes

  1. Ashley L. St. John

    Present address: Present addresses: Program in Emerging Infectious Diseases, Duke–National University of Singapore, Graduate Medical School, Level 9, Khoo Teck Puat Building, 8 College Road, Singapore 169857, Singapore; Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA,

Authors and Affiliations

  1. Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA

    Ashley L. St. John, Herman F. Staats & Soman N. Abraham

  2. Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA

    Cheryl Y. Chan, Herman F. Staats & Soman N. Abraham

  3. Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA

    Herman F. Staats

  4. Department of Biomedical Engineering, Duke University Medical Center, Durham, North Carolina 27710, USA

    Kam W. Leong

  5. Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA

    Soman N. Abraham

  6. Program in Emerging Infectious Diseases, Duke–National University of Singapore, Singapore 169857, Singapore

    Soman N. Abraham

Authors
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Contributions

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). https://doi.org/10.1038/nmat3222

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