Baert, Kim

Cox, Eric

De Geest, Bruno

Devriendt, Bert

English

Ghent University Academic Bibliography

Yeast	  particles	  targeted	  to	  APN	  as	  antigen	  delivery	  system	  to	  porcine	  immune	  cells	  Kim	  Baerta,	  Bert	  Devriendta,	  Bruno	  De	  Geestb,	  Eric	  Coxa	  	  aLaboratory	  of	  Immunology,	  Faculty	  of	  Veterinary	  Medicine,	  Ghent	  University,	  Belgium	  	  bLaboratory	  of	  Pharmaceutical	  Technology,	  Faculty	  of	  Pharmaceutical	  Sciences,	  Ghent	  University,	  Belgium	  	  Abstract	  Neonatal	  and	  newly	  weaned	  piglets	  are	  highly	  susceptible	  to	  enterotoxigenic	  E.	  coli	  (ETEC)	  infections,	  which	   cause	   huge	   economical	   losses	   in	   the	   pig	   industry.	   Oral	   vaccination	   seems	   to	   be	   the	   most	  efficient	   and	   economic	   strategy	   to	   prevent	   intestinal	   diseases.	   Current	   oral	   vaccines	   include	   live	  attenuated	  or	  inactivated	  organisms	  have	  been	  widely	  used,	  however,	  they	  are	  often	  inadequate	  or	  have	   known	   safety	   issues.	   The	   implementation	   of	   safer	   recombinant	   subunit	   vaccines	   is	   currently	  under	   investigation,	   however,	   the	   development	   of	   effective	   vaccine	   subunits	   encounters	   multiple	  challenges,	   such	   as	   instability	   and	   limited	   immunogenicity.	   The	   encapsulation	   of	   antigens	   in	  microparticles	  is	  a	  promising	  approach	  to	  overcome	  these	  problems,	  as	  they	  can	  protect	  the	  antigens	  against	   degradation	   as	   well	   as	   carry	   potent	   adjuvants	   or	   immune	   modulators	   to	   enhance	   the	  immunogenicity.	  Yeast	  particles	  (YP)	  are	  innovative	  hollow	  and	  porous	  microparticles	  consisting	  of	  a	  β-­‐glucan	   cell	   wall.	   Β-­‐glucans	   are	   key	   constituents	   of	   the	   cell	   walls	   of	   fungi	   and	   major	   ‘microbe-­‐associated	  molecular	  pattern’	  (MAMPs).	  These	  MAMPs	  are	  very	  interesting	  in	  the	  development	  of	  a	  vaccine	  for	  their	  adjuvant	  effect	  on	  the	  immune	  system,	  resulting	  in	  the	  activation	  of	  dendritic	  cells	  (DCs),	   the	   secretion	   of	   specific	   cytokines/chemokines	   and	   oxidative	   burst	   generation.	   In	   addition,	  these	  microparticles	   can	  be	  engineered	   to	   target	   receptors	   located	  on	  enterocytes	   to	  enhance	   the	  translocation	   of	   the	   particles	   through	   the	   epithelial	   barrier.	  We	   aimed	   to	   evaluate	   the	   capacity	   of	  these	  yeast	  particles	  as	  oral	  antigen	  delivery	  system.	  First,	  we	  loaded	  the	  hollow	  yeast	  particles	  with	  BSA-­‐FITC	  as	  antigen	  model	   and	   investigated	   the	  adjuvanticity	  of	   these	  particles.	  We	  demonstrated	  that	   these	   particles	   are	   able	   to	   stimulate	   the	   antimicrobial	   response	   of	   neutrophils.	   Next,	   we	  targeted	  these	  particles	  to	  aminopeptidase	  N	  (APN),	  which	  is	  a	  very	  interesting	  target	  by	  its	  location	  on	  intestinal	  epithelial	  cells	  as	  well	  as	  on	  immune	  cells.	  The	  effect	  of	  these	  APN-­‐targeted	  particles	  on	  porcine	   cells	   was	   analysed.	   Targeting	   to	   APN	   resulted	   in	   an	   enhanced	   endocytosis	   by	   intestinal	  epithelial	   cells	   and	   by	   monocyte-­‐derived	   dendritic	   cells	   (MoDCs).	   Moreover,	   these	   APN-­‐targeted	  particles	   were	   able	   to	   increase	   the	   antimicrobial	   activity	   response	   in	   porcine	   neutrophils.	   These	  findings	   suggests	   that	   targeting	  of	   yeast	   particles	   to	  APN	   is	   an	   efficient	  way	   to	   deliver	   antigens	   to	  immune	  cells	  located	  in	  the	  intestinal	  mucosa.	  	  

Yeast particles targeted to APN as antigen delivery system to porcine immune cells

https://biblio.ugent.be/publication/4146680/file/4146688

Yeast particles targeted to APN as antigen delivery system to porcine immune cells

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