Polymeric multilayer capsule-mediated vaccination induces protective immunity against cancer and viral infection.
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-γ 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-1β. Finally, using DC-depleted mice, we have identified DCs as the key mediators of the immunogenic properties of PMLC.
Laboratory of Pharmaceutical Technology, Department of PharmaceuticsGhent University, Ghent, Belgium. br.degeest@ugent.be
Bruno G
BG
De Geest
Monique A
MA
Willart
Hamida
H
Hammad
Bart N
BN
Lambrecht
Charlotte
C
Pollard
Pieter
P
Bogaert
Marina
M
De Filette
Xavier
X
Saelens
Chris
C
Vervaet
Jean Paul
JP
Remon
Johan
J
Grooten
Stefaan
S
De Koker
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology; D001672:Biocompatible Materials / Q000737:chemistry; D002214:Capsules; D016264:Dextran Sulfate / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology; D058847:Inflammasomes / Q000378:metabolism; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control*; D008546:Melanoma, Experimental / Q000276:immunology* / Q000517:prevention & control*; D051379:Mice; D010455:Peptides / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D014611:Vaccination / Q000379:methods*
D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D001672:Biocompatible Materials; D002214:Capsules; D004337:Drug Carriers; D058847:Inflammasomes; D010455:Peptides; D011108:Polymers; C015462:polyarginine; D016264:Dextran Sulfate