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Polymeric multilayer capsule-mediated vaccination induces protective immunity against cancer and viral infection

Bruno De Geest (UGent), Monique Willart (UGent), Hamida Hammad (UGent), Bart Lambrecht (UGent), Charlotte Pollard (UGent), Pieter Bogaert (UGent), Marina De Filette (UGent), Xavier Saelens (UGent), Chris Vervaet (UGent), Jean Paul Remon (UGent), et al.
(2012) ACS NANO. 6(3). p.2136-2149
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Abstract
Recombinant antigens hold high potential to develop vaccines against lethal intracellular pathogens and cancer. However, they are poorly immunogenic and fail to induce potent cellular immunity. In this paper, we demonstrate that polymeric multilayer capsules (PMLC) strongly increase antigen delivery toward professional antigen-presenting cells in vivo, including dendritic cells (DCs), macrophages, and B cells, thereby enforcing antigen presentation and stimulating T cell proliferation. A thorough analysis of the T cell response demonstrated their capacity to induce IFN-gamma secreting CD4 and CD8 T cells, in addition to follicular T-helper cells, a recently identified CD4 T cell subset supporting antibody responses. On the B cell level, PMLC-mediated antigen delivery promoted the formation of germinal centers, resulting in increased numbers of antibody-secreting plasma cells and elevated antibody titers. The functional relevance of the induced immune responses was validated in murine models of influenza and melanoma. On a mechanistic level, we have demonstrated the capacity of PMLC to activate the NALP3 inflammasome and trigger the release of the potent pro-inflammatory cytokine IL-1 beta. Finally, using DC-depleted mice, we have identified DCs as the key mediators of the immunogenic properties of PMLC.
Keywords
vaccines, polyelectrolytes, capsules, self-assembly, layer-by-layer, dendritic cells, DENDRITIC CELLS, POLYELECTROLYTE MICROCAPSULES, INFLUENZA-A, IN-VIVO, PROTEIN ENCAPSULATION, ANTIGEN PRESENTATION, CROSS-PRESENTATION, MATRIX PROTEIN-2, NEXT-GENERATION, INNATE IMMUNITY

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Chicago
De Geest, Bruno, Monique Willart, Hamida Hammad, Bart Lambrecht, Charlotte Pollard, Pieter Bogaert, Marina De Filette, et al. 2012. “Polymeric Multilayer Capsule-mediated Vaccination Induces Protective Immunity Against Cancer and Viral Infection.” Acs Nano 6 (3): 2136–2149.
APA
De Geest, Bruno, Willart, M., Hammad, H., Lambrecht, B., Pollard, C., Bogaert, P., De Filette, M., et al. (2012). Polymeric multilayer capsule-mediated vaccination induces protective immunity against cancer and viral infection. ACS NANO, 6(3), 2136–2149.
Vancouver
1.
De Geest B, Willart M, Hammad H, Lambrecht B, Pollard C, Bogaert P, et al. Polymeric multilayer capsule-mediated vaccination induces protective immunity against cancer and viral infection. ACS NANO. 2012;6(3):2136–49.
MLA
De Geest, Bruno, Monique Willart, Hamida Hammad, et al. “Polymeric Multilayer Capsule-mediated Vaccination Induces Protective Immunity Against Cancer and Viral Infection.” ACS NANO 6.3 (2012): 2136–2149. Print.
@article{3129366,
  abstract     = {Recombinant antigens hold high potential to develop vaccines against lethal intracellular pathogens and cancer. However, they are poorly immunogenic and fail to induce potent cellular immunity. In this paper, we demonstrate that polymeric multilayer capsules (PMLC) strongly increase antigen delivery toward professional antigen-presenting cells in vivo, including dendritic cells (DCs), macrophages, and B cells, thereby enforcing antigen presentation and stimulating T cell proliferation. A thorough analysis of the T cell response demonstrated their capacity to induce IFN-gamma secreting CD4 and CD8 T cells, in addition to follicular T-helper cells, a recently identified CD4 T cell subset supporting antibody responses. On the B cell level, PMLC-mediated antigen delivery promoted the formation of germinal centers, resulting in increased numbers of antibody-secreting plasma cells and elevated antibody titers. The functional relevance of the induced immune responses was validated in murine models of influenza and melanoma. On a mechanistic level, we have demonstrated the capacity of PMLC to activate the NALP3 inflammasome and trigger the release of the potent pro-inflammatory cytokine IL-1 beta. Finally, using DC-depleted mice, we have identified DCs as the key mediators of the immunogenic properties of PMLC.},
  author       = {De Geest, Bruno and Willart, Monique and Hammad, Hamida and Lambrecht, Bart and Pollard, Charlotte and Bogaert, Pieter and De Filette, Marina and Saelens, Xavier and Vervaet, Chris and Remon, Jean Paul and Grooten, Johan and De Koker, Stefaan},
  issn         = {1936-0851},
  journal      = {ACS NANO},
  keyword      = {vaccines,polyelectrolytes,capsules,self-assembly,layer-by-layer,dendritic cells,DENDRITIC CELLS,POLYELECTROLYTE MICROCAPSULES,INFLUENZA-A,IN-VIVO,PROTEIN ENCAPSULATION,ANTIGEN PRESENTATION,CROSS-PRESENTATION,MATRIX PROTEIN-2,NEXT-GENERATION,INNATE IMMUNITY},
  language     = {eng},
  number       = {3},
  pages        = {2136--2149},
  title        = {Polymeric multilayer capsule-mediated vaccination induces protective immunity against cancer and viral infection},
  url          = {http://dx.doi.org/10.1021/nn205099c},
  volume       = {6},
  year         = {2012},
}

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