Baert, Kim

Cox, Eric

De Geest, Bruno

Devriendt, Bert

English

Ghent University Academic Bibliography

Title: β-glucan microparticles targeted to APN as mucosal antigen delivery system in oral vaccination of piglets against ETEC infections  Authors & affiliations: Kim Baerta, Bruno De Geestb, Bert Devriendta, Eric Coxa aDepartment of Immunology, Ghent University, Belgium bDepartment of Pharmaceutics, Ghent University, Belgium  Abstract:  (Your abstract must use Normal style and must fit in this box.  Your abstract should be no longer than 300 words.  Enterotoxigenic	  Escherichia	   coli	  (ETEC)	   cause	   diarrhea	   in	   neonatal	   and	   newly	  weaned	  piglets,	  resulting	  in	  economic	  losses	  due	  to	  growth	  retardation,	  increased	  drug	  use	  and	  elevated	  mortality.	  Neonatal	  infections	  can	  be	  prevented	  by	  a	  passive	  lactogenic	   immunity	   obtained	   by	   vaccination	   of	   the	   sow,	   however,	   this	   passive	  protection	   disappears	   at	   the	   moment	   of	   weaning.	   To	   control	   post-­‐weaning	  diarrhea,	  oral	  vaccination	   is	  a	  promising	  strategy,	   since	  vaccines	  delivered	   to	   the	  mucosal	  intestinal	  tract	  can	  elicit	  immune	  responses	  at	  the	  site	  of	  pathogen	  entry.	  Moreover,	  oral	  vaccination	  has	  many	  physiological	  and	  practical	  advantages,	  such	  as	  decreased	  costs	  and	  relative	  ease	  of	  administration	  without	  the	  risk	  of	  needle-­‐stick	  injuries.	  Unfortunately,	  developing	  oral	  subunit	  vaccines	  has	  been	  challenging	  due	  to	  numerous	  potential	  obstacles,	  such	  as	  a	  hostile	  environment	  of	  the	  gastro-­‐intestinal	   tract,	   oral	   tolerance	   and	   the	   epithelial	   barrier.	   Therefore,	   antigen	  delivery	   systems	   in	   combination	   with	   selective	   targeting	   are	   an	   appealling	  approach	  to	  develop	  potent	  oral	  vaccines.	  The	  current	  study	  evaluated	  the	  capacity	  of	   aminopeptidase	   N	   (APN)-­‐targeted	   β-­‐glucan	   microparticles	   as	   oral	   delivery	  system.	   Antibodies	   against	   APN,	   an	   apical	   intestinal	   epithelial	   receptor,	   were	  conjugated	  to	  β-­‐glucan	  microparticles	  via	  the	  biolinker	  protein	  G,	  which	  leads	  to	  a	  correct	  orientation	  of	   the	  antibodies.	  The	   resultant	  microparticles	  were	  analysed	  for	  their	  antigen	  encapsulation,	  adjuvanticity	  and	  interaction	  with	  enterocytes	  and	  dendritic	  cells	  (DCs).	  Targeting	  to	  APN	  is	  an	  efficacious	  way	  to	  increase	  the	  uptake	  of	  microparticles	  by	  enterocytes	   in	   vitro	   (IPEC-­‐J2)	   and	  ex	   vivo	   (porcine	   intestinal	  explants).	   In	   addition,	   APN-­‐targeted	   β-­‐glucan	   microparticles	   are	   highly	  phagocytosed	   by	   DCs,	   which	   leads	   to	   the	   upregulation	   of	   DC	   activation	  markers	  CD25	   and	   CD40	   and	   to	   a	   strong	   pro-­‐inflammatory	   cytokine	   response.	   Finally,	  conjugation	   of	   β-­‐glucan	   microparticles	   with	   antibodies	   neither	   impeded	   antigen	  encapsulation	   nor	   adjuvanticity.	   Taken	   together,	   these	   data	   support	   the	   use	   of	  APN-­‐targeted	   β-­‐glucan	   microparticles	   for	   oral	   delivery	   of	   enteric	   pathogen	  antigens	  and	  motivate	  further	  in	  vivo	  research	  of	  these	  promising	  antigen	  carriers.	      

β-glucan microparticles targeted to APN as mucosal antigen delivery system in oral vaccination of piglets against ETEC infections

https://biblio.ugent.be/publication/6955911/file/6955916.pdf

β-glucan microparticles targeted to APN as mucosal antigen delivery system in oral vaccination of piglets against ETEC infections

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