Page 13 - 80_02
P. 13

Carlos	
  Alonso,	
  Manuel	
  Soto	
  

	
  
commercial	
   vaccines	
   against	
   canine	
   leishmaniasis:	
   Leishmune	
   (based	
   on	
   Parasite	
  
Fucose-­-Manose-­-Ligand)	
  (12),	
  Leishtec,	
  based	
  on	
  a	
  recombinant	
  amastigote	
  antigen	
  
namely	
   A2	
   protein	
   (13)	
   and	
   CaniLeish,	
   composed	
   on	
   promastigotes	
   secreted-­-
excreted	
   factors	
   (14,	
   15).	
   In	
   spite	
   of	
   the	
   existence	
   of	
   these	
   products,	
   the	
   search	
   of	
  
molecules	
   for	
   development	
   of	
   Leishmania	
   vaccines	
   continues,	
   looking	
   for	
  
improving	
   protection	
   against	
   different	
   forms	
   of	
   leishmaniasis.	
   There	
   are	
   recent	
  
review	
   articles	
   covering	
   the	
   progress	
   made	
   towards	
   the	
   development	
   of	
  
Leishmania	
  vaccines,	
  including	
  some	
  of	
  the	
  most	
  studied	
  parasite	
  proteins	
  together	
  
with	
  the	
  effect	
  of	
  various	
  adjuvants	
  employed	
  in	
  experimental	
  vaccination	
  trials	
  (4,	
  
11,	
   16-­-22).	
   There	
   is	
   general	
   consensus	
   indicating	
   that	
   the	
   establishment	
   of	
   a	
  
protective	
  anti-­-Leishmania	
  response	
  may	
  require	
  the	
  induction	
  of	
  parasite	
  specific	
  
long-­-lasting	
  memory	
  T	
  cells	
  that	
  will	
  expand	
  as	
  effector	
  T	
  cells	
  for	
  the	
  production	
  
of	
   IFN-­-gamma	
   dependent	
   responses	
   specific	
   for	
   parasite	
   antigens	
   in	
   order	
   to	
  
activate	
  the	
  leishmanicidal	
  capacities	
  of	
  infected	
  macrophages.	
  In	
  this	
  way,	
  most	
  of	
  
the	
   recent	
   research	
   is	
   focused	
   on	
   the	
   identification	
   of	
   the	
   Leishmania	
   molecules	
  
that	
   interacts	
   with	
   the	
   host	
   immune	
   system	
   and	
   on	
   the	
   analysis	
   of	
   their	
  
prophylactic	
   properties	
   when	
   immunized	
   in	
   experimental	
   models	
   of	
   infection	
   as	
  
second	
  generation	
  vaccines	
  (based	
  on	
  parasite	
  fractions	
  or	
  recombinant	
  proteins)	
  
or	
  third	
  generation	
  vaccines	
  (mainly	
  DNA-­-based	
  vaccines).	
  In	
  this	
  work	
  we	
  make	
  a	
  
review	
   of	
   these	
   studies	
   performed	
   with	
   different	
   parasite	
   proteins,	
  
immunodominant	
   antigens	
   during	
   infection,	
   focusing	
   on	
   the	
   results	
   obtained	
  
taking	
  into	
  consideration	
  the	
  implication	
  of	
  different	
  Spanish	
  researchers,	
  alone	
  or	
  
in	
  collaborative	
  work,	
  in	
  order	
  to	
  show	
  the	
  important	
  efforts	
  made	
  in	
  our	
  country	
  
during	
  the	
  last	
  years,	
  helping	
  to	
  mitigate	
  the	
  effects	
  of	
  this	
  emerging	
  disease.	
  	
  

2.	
  LEISHMANIA	
  SURFACE	
  ANTIGENS	
  

        A	
   number	
   of	
   surface	
   glycoproteins	
   are	
   present	
   in	
   promastigote	
   forms	
   of	
  
Leishmania	
   parasites.	
   The	
   Leishmania	
   proteinase	
   GP63,	
   one	
   of	
   the	
   most	
   abundant	
  
surface-­-exposed	
  proteins	
  on	
  parasite	
  promastigotes	
  (23,	
  24)	
  has	
  been	
  described	
  as	
  
an	
   immunogenic	
   protein	
   during	
   human	
   VL	
   (25).	
   The	
   GP63	
   is	
   also	
   an	
   antigenic	
  
molecule	
  in	
  canine	
  VL,	
  as	
  described	
  by	
  (26).	
  Using	
  a	
  recombinant	
  version	
  of	
  the	
  L.	
  
infantum	
   GP63	
   (LiGP63)	
   as	
   well	
   as	
   some	
   synthetic	
   peptides	
   derived	
   from	
   its	
  
aminoacid	
  sequence,	
  Dr.	
  Alonso’s	
  laboratory	
  (Centro	
  de	
  Biología	
  Molecular	
  Severo	
  
Ochoa,	
   CSIC-­-UAM)	
   was	
   able	
   to	
   demonstrate	
   that	
   LiGP63	
   was	
   recognized	
   by	
   the	
  
100%	
   of	
   the	
   sera	
   from	
   L.	
   infantum	
   infected	
   dogs	
   and	
   that	
   the	
   C-­-terminal	
   domain	
  
was	
  the	
  most	
  antigenic	
  region	
  of	
  the	
  protein.	
  On	
  the	
  basis	
  of	
  its	
  surface	
  localization	
  
and	
   its	
   antigenicity,	
   second	
   generation	
   vaccines	
   related	
   with	
   GP63	
   and	
   its	
  
immunodominant	
   epitopes	
   have	
   been	
   extensively	
   studied	
   as	
   vaccine	
   candidates	
  
using	
  murine	
  models	
  of	
  infection	
  (Revised	
  in	
  (27)).	
  Of	
  special	
  interest	
  is	
  the	
  work	
  
published	
   by	
   Cote-­-Sierra	
   and	
   coworkers	
   (28)	
   with	
   the	
   collaboration	
   of	
   Dr..	
  

252	
  

	
  
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