Dr. Michael Murtaugh and Dr. Cheryl Dvorak - Natural Infection, Immunity & Prevalence of PCV2

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Natural Infection, Immunity & Prevalence of PCV2 - Dr. Michael Murtaugh and Dr. Cheryl Dvorak, University of Minnesota, USA , from the Boehringer Ingelheim Pre-AASV Conference, February 28, 2014 - …

Natural Infection, Immunity & Prevalence of PCV2 - Dr. Michael Murtaugh and Dr. Cheryl Dvorak, University of Minnesota, USA , from the Boehringer Ingelheim Pre-AASV Conference, February 28, 2014 - Dallas, TX

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  • 1. Natural  Infec-on,  Immunity  &  Prevalence  of  PCV2     Michael  Murtaugh  and  Cheryl  Dvorak   University  of  Minnesota,  USA   Acknowledgements   Charles  Haley  and  Eric  Bush,  USDA-­‐APHIS   Suresh  Tikoo,  VIDO   Sponsors   University  of  Minnesota  SDEC   Boehringer  Ingelheim  Vetmedica,  Inc.    
  • 2. Canada  1999   mPCV2b   PCV2a   2001-­‐2013   PCV2b   2003-­‐2013   2006-­‐2013   China  2003     2012-­‐2013   MN  VDL  Sequencing   917  Isolates   0.02 0.5   5   50   500   1   3   5   7   9   11   13   15   Series1   1999   2001   2003   2005   2007   2009   2011   2013   Number  of  Sequences   Year  of  Isola-on   490  
  • 3. Swine  Finishing  Herds  in  USA  (n=187,  pigs  >20  weeks)   Viremia   PCV2  >99%  of  Herds  Posi-ve   An-body   >99%  of  Herds  Posi-ve   Average  PCV2  -ter  >104  copies  per  ml   0   50   100   Within  Herd  Prevalence   Frequency  (Number  of  Farms)   0   100   200   300   400   500   600   2   3   4   5   6   7   8   9   PCV2  DNA  copies/ml  (log )   Frequency  (number  of  animals)   0   20   40   60   80   0-­‐10   11-­‐20   21-­‐30   31-­‐40   41-­‐50   51-­‐60   61-­‐70   71-­‐80   81-­‐90   91-­‐100   Within  Herd  Prevalence   Frequency  (Number  of  Farms)   In  2005,  there  was  no  PCVAD  in  the  USA   Porcine  Circovirus  in  2006,  USA  
  • 4. Porcine  Circovirus  in  2006  Pre-­‐PCVAD,  Pre-­‐Vaccines   Swine  Finishing  Herds  in  USA  (n=187,  pigs  >20  weeks)   Viremia   PCV2  >99%  of  Herds  Posi-ve   An-body   >99%  of  Herds  Posi-ve   Average  PCV2  -ter  >104  copies  per  ml   0   50   100   Within  Herd  Prevalence   Frequency  (Number  of  Farms)   0   100   200   300   400   500   600   2   3   4   5   6   7   8   9   PCV2  DNA  copies/ml  (log )   Frequency  (number  of  animals)   0   20   40   60   80   0-­‐10   11-­‐20   21-­‐30   31-­‐40   41-­‐50   51-­‐60   61-­‐70   71-­‐80   81-­‐90   91-­‐100   Within  Herd  Prevalence   Frequency  (Number  of  Farms)   Puvanendiran  et  al.  2011.   Virus  Res  157:92-­‐98.  
  • 5. 0 50 100 150 200 250 300 350 400 A B AB - 286 386 95 233 N=1000 PCV2a PCV2b PCV2a+ PCV2b Negative 29% 39% 9% 23% PCV2b  in  48%  of  pigs   PCV2a  in  38%  of  pigs   :  in  2006   PCV2 a   PCV2 b   qPCR   Rowland  et  al.  
  • 6. AB   B   A  Number  per  bin   CT  value   X=35.3   X=35.9   X=34.4   Level  of  Viremia  is   Not  Affected  by   Genotype  of   Infec-ng  Viruses     Infec-on  with   PCV2a=PCV2b=   PCV2a+2b  
  • 7. •  Pigs  at  finishing  are  viremic   •  An-body  is  not  controlling  infec-on   •  What  is  the  source  of  infec-on?   When  do  Pigs  get  Infected?  
  • 8. Sows are viremic Virus in Colostrum Virus in Oral fluids Pre-­‐farrowing  Sows  are  Infected  and  Shed  PCV2   No effect of parity
  • 9. •  Serum  and  swabs  were  collected  pre-­‐suckling   •  78%  of  piglets  were  born  viremic   •  All  PCR-­‐posi-ve  samples  were  PCV2b  (n=219)   Serum Piglets  are  born  Viremic   Skin Swabs
  • 10. PCV2 is present in pre- suckling piglet serum •  Non-­‐viremic  sows  on  Farms  2,   3,  5,  and  6  gave  birth  to   viremic  piglets.   •  Sows  are  PCV2  posi-ve  even   in  the  absence  of  observable   viremia.   Nonviremic  Sows  Produce  Viremic  Piglets   A  Nega-ve  PCR  Test  is  not  Proof  of  Nega-ve  
  • 11. Piglet  skin   qPCR  Detects  Live,  Infec-ous  Virus  in  Pigs  and   Environment,  Except  on  Sani-zed  Surfaces   Piglet  serum  Sow  Serum   Crate  Bar  
  • 12. Serum IgG •  An--­‐PCV2  an-bodies  are  present  in  serum,  colostrum,  and  oral  fluids  of  sows   •  Sows  from  farm  3  and  5  were  vaccinated  and  have  universally  high  an-bodies   Colostrum IgG Sows  have  High  Levels  of  an--­‐PCV2  An-bodies  
  • 13. PCV2  Infec-on  is  Persistent   •  Even  in  the  presence  of  PCV2-­‐specific  an-bodies,   PCV2  viremia  is  maintained.   •  Once  an  animal  is  infected,  it  is  infected  for  life.   0   20   40   60   80   100   0   5   10   15   20   25   %  PCV2  posi-ve  pigs   Piglet  age  (weeks)   Viral  DNA  levels   Sow   Piglets   0   1   2   3   0   5   10   15   20   25   Average  OD  value   Piglet  age  (weeks)   IgG  An-body  levels   Sow   Piglets  
  • 14. Persistent  infec-on:  Vaccina-on  Evidence   Young pigs (45 kg) Old pigs (100 kg) January neg* neg March neg neg May 104 107 June neg neg August neg neg October neg neg November neg neg January neg neg One batch not vaccinated Vaccination can suppress viremia to non-detectable levels. However, virus reappeared when vaccination was stopped. Vaccination does not cure infection.
  • 15. •  The  farrowing  environment  is  thoroughly  contaminated   with  PCV2.   •  Growing  piglets  are  under  constant  viral  challenge  from  the   environment  and  from  the  sow.     •  Piglets  can  be  infected  with  PCV2  in  utero,  during  birth,  and   from  the  environment.   virus Maternal Ab piglet antibodies 10-15 weeks Pigs  are  Infected  at  Birth  -­‐  Infec-on  can  be  Lifelong  
  • 16. Six  Years  Later:  What  is  the  PCV2  Status   A B AB A B AB 102 103 104 105 106 107 108 109 1010 Viralcopies/ml 2006 2012 Viral  loads  are  reduced.  
  • 17. 0   10   20   30   40   50   60   70   80   90   Posi-ve   Nega-ve   %  PCV2  posi-ve  pigs   Large  Increase  in  PCR-­‐nega-ve  pigs   2006   2012   Change  in  PCR  Status  2006  -­‐  2012  
  • 18. a" " b" c" " d" An--­‐Rep   An--­‐Cap   Infected  +  Vaccinated  81%   Vaccinated  Only  13%   Background   noise  3%   Nega-ve  3%   Serological  Status  of  Finishing  Pigs  -­‐  2012  
  • 19. Vaccina-on  Suppresses  but  does  not  Cure  Infec-on   Young pigs (45 kg) Old pigs (100 kg) January neg* neg March neg neg May 104 107 June neg neg August neg neg October neg neg November neg neg January neg neg One batch not vaccinated Vaccination can suppress viremia to non-detectable levels. However, virus reappeared when vaccination was stopped.
  • 20. Conclusion:  PCV2  causes  disease,  but  presence  in  lymph  nodes  does  not                                              prevent  immune  response  to  PCV2  vaccina-on.     Kristensen  et  al.  2011.  Prev  Vet  Med  98:250.   Vaccina-on  Works:  Meta-­‐Analysis  (66  trials)   Vaccines  against  PCV2  improve  growth     Vaccines  against  PCV2  reduce  mortality  
  • 21. How  is  vaccina-on  working????????????   §  No  one  really  knows  the  mechanism.   §  Vaccines  do  not  induce  robust  an-body  response.   §  Neutralizing  an-bodies  exist  but  do  not  eliminate  virus.   §  Cytotoxic  T  cells  not  a  general  feature  of  protein  vaccines.   §  But,  no  ques-on  that  it  works.    
  • 22. Concluding  Observa-ons   v PCV2  is  a  highly  conserved  virus  displaying  limited  gene-c   diversity  in  the  United  States   v PCV2  is  endemic  is  swine  herds;  PCV2b  is  more  common   than  PCV2a.   v PCV2  exposure  starts  at  birth;  infec-on  can  be  lifelong.     v Vaccina-on  effec-vely  controls  PCVAD  and  reduces   infec-ous  pressure,  but  does  not  eliminate  virus.