Baert, Kim

Cox, Eric

De Geest, Bruno

Devriendt, Bert

Dierendonck, Marijke

Favoreel, Herman

Remon, Jean Paul

English

Ghent University Academic Bibliography

Polyelectrolyte	  microparticles	  as	  biomimetic	  mucosal	  delivery	  vehicles	  facilitate	  antigen	  presentation	  by	  dendritic	  cells	  	  Bert	  DEVRIENDT1,*,	  Kim	  BAERT1,	  Marijke	  DIERENDONCK2,	  Herman	  FAVOREEL1,	  Jean	  Paul	  REMON2,	  Bruno	  G.	  DE	  GEEST2,	  Eric	  COX1	  	  1Laboratory	  of	  Immunology,	  Faculty	  of	  Veterinary	  Medicine,	  Ghent	  University,	  Merelbeke;	  2Laboratory	  of	  Pharmaceutical	  Technology,	  Department	  of	  Pharmaceutics,	  Faculty	  of	  Pharmaceutical	  Sciences,	  Ghent	  University,	  Ghent	  	  Vaccination	  is	  regarded	  as	  the	  most	  efficient	  and	  cost-­‐effective	  way	  to	  prevent	  infectious	  diseases.	  Vaccine	  design	  nowadays	  focuses	  on	  the	   implementation	  of	  safer	  recombinant	  subunit	  vaccines.	  However,	  these	  recombinant	  subunit	  antigens	  are	  often	  poor	  immunogens	  and	  several	  strategies	  are	   currently	   under	   investigation	   to	   enhance	   their	   immunogenicity.	   The	   encapsulation	   of	   the	  antigens	  in	  biodegradable	  microparticulate	  delivery	  systems	  seems	  a	  promising	  strategy	  to	  boost	  their	   immunogenicity.	  Here,	  we	  evaluate	   the	  capacity	  of	  polyelectrolyte	  microparticles	  (PECMs),	  fabricated	  by	  single	  step	  spray-­‐drying,	  to	  deliver	  antigens	  to	  porcine	  dendritic	  cells	  (DCs)	  and	  how	  these	  particles	  affect	  their	  functional	  maturation.	  As	  clinically	  relevant	  model	  antigen	  F4	  fimbriae,	  a	   bacterial	   adhesin	   purified	   from	   a	   porcine-­‐specific	   enterotoxigenic	   E.	   coli	   (ETEC)	   strain,	   was	  chosen.	   PECMs	   were	   loaded	   with	   the	   F4	   fimbriae	   by	   co-­‐spray-­‐drying	   these	   antigens	   with	   the	  polyelectrolytes	   dextran-­‐sulphate	   and	   poly-­‐L-­‐arginine	   and	   the	   sacrificial	   template	   mannitol.	  SIRPα+	   monocytes	   were	   enriched	   from	   peripheral	   blood	   by	   immunomagnetic	   selection	   and	  cultured	  with	  IL-­‐4	  and	  GM-­‐CSF	  to	  generate	  porcine	  monocyte-­‐derived	  DCs	  (MoDCs).	  These	  in	  vitro	  generated	   immature	   MoDCs	   were	   incubated	   with	   F4	   fimbriae	   or	   F4-­‐fimbriae-­‐loaded	  polyelectrolyte	   microparticles	   (F4-­‐PECMs)	   and	   their	   maturation	   was	   assessed	   by	   confocal	   and	  live	  cell	   imaging,	   flow	  cytometry,	  T-­‐cell	  proliferation	  assays	  and	  cytokine	  ELISAs.	  The	  F4-­‐PECMs	  were	   efficiently	   internalised	   by	   porcine	   MoDCs	   and	   enhanced	   the	   expression	   of	   DC	   activation	  markers.	   This	   phenotypical	   maturation	   correlated	   with	   an	   increased	   secretion	   of	   the	   pro-­‐inflammatory	   cytokines	   IL-­‐6	   and	   IL-­‐1β.	   More	   importantly,	   F4-­‐PECMs	   elevated	   the	   T-­‐cell	  stimulatory	  ability	  and	  antigen	  presentation	  capacity	  to	  CD6+	  T-­‐cells	  of	  MoDCs.	  Moreover,	  PECMs	  efficiently	  promoted	  the	  CD8+	  T-­‐cell	  stimulatory	  activity	  of	  dendritic	  cells,	  indicating	  an	  enhanced	  ability	  of	  the	  DCs	  to	  cross	  present	  the	  encapsulated	  antigens	  via	  MHCI.	  In	  conclusion,	  single	  step	  spray-­‐dried	   antigen-­‐loaded	   polyelectrolyte	   microparticles	   efficiently	   enhanced	   the	   functional	  maturation	   and	   increased	   the	   cross-­‐presentation	   ability	   of	   porcine	   DCs.	   Our	   results	   confirm	  recent	   data	   obtained	   in	   rodent	  models	   that	   these	   PECMs	   boost	   the	   immunogenicity	   of	   vaccine	  antigens.	  In	  addition,	  this	  antigen	  delivery	  system	  allows	  not	  only	  the	  co-­‐encapsulation	  of	  immune	  potentiators,	  such	  as	  PRR	  ligands,	  but	  also	  the	  functionalisation	  of	  the	  microparticles’	  surface	  with	  targeting	   ligands	   to	   enhance	   the	   delivery	   of	   these	   carrier	   systems	   to	   the	   immune	   system.	   Our	  results	   could	   accelerate	   the	   development	   of	   veterinary	   and	   human	   subunit	   vaccines	   based	   on	  polyelectrolyte	  microparticulate	  delivery	  systems	  to	  combat	  a	  variety	  of	  extra-­‐	  and	   intracellular	  pathogens.	   

Polyelectrolyte microparticles as biomimetic mucosal delivery vehicles facilitate antigen presentation by dendritic cells

https://biblio.ugent.be/publication/4146690/file/4146698

Polyelectrolyte microparticles as biomimetic mucosal delivery vehicles facilitate antigen presentation by dendritic cells

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Ghent University Academic Bibliography