Natural Infection, Immunity & Prevalence of PCV2
Michael Murtaugh and Cheryl Dvorak
University of Minnesota, USA
Acknowled...
Canada 1999
mPCV2b
PCV2a
2001-2013
PCV2b
2003-2013
2006-2013
China 2003
2012-2013
MN VDL Sequencing
917 Isolates
0.02
0.5
...
Swine Finishing Herds in USA (n=187, pigs >20 weeks)
Viremia
PCV2 >99% of Herds Positive
Antibody
>99% of Herds Positive
A...
Porcine Circovirus in 2006 Pre-PCVAD, Pre-Vaccines
Swine Finishing Herds in USA (n=187, pigs >20 weeks)
Viremia
PCV2 >99% ...
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 ...
AB
B
ANumberperbin
CT value
X=35.3
X=35.9
X=34.4
Level of Viremia is
Not Affected by
Genotype of
Infecting Viruses
Infecti...
• Pigs at finishing are viremic
• Antibody is not controlling infection
• What is the source of infection?
When do Pigs ge...
Sows are viremic
Virus in Colostrum Virus in Oral fluids
Pre-farrowing Sows are Infected and Shed PCV2
No effect of parity
• Serum and swabs were collected pre-suckling
• 78% of piglets were born viremic
• All PCR-positive samples were PCV2b (n=...
PCV2 is present in pre-
suckling piglet serum
• Non-viremic sows on Farms
2, 3, 5, and 6 gave birth to
viremic piglets.
• ...
Piglet skin
qPCR Detects Live, Infectious Virus in Pigs and
Environment, Except on Sanitized Surfaces
Piglet serumSow Seru...
Serum IgG
• Anti-PCV2 antibodies are present in serum, colostrum, and oral fluids of sows
• Sows from farm 3 and 5 were va...
PCV2 Infection is Persistent
• Even in the presence of PCV2-specific
antibodies, PCV2 viremia is maintained.
• Once an ani...
Persistent infection: Vaccination Evidence
Young pigs
(45 kg)
Old pigs
(100 kg)
January neg* neg
March neg neg
May 104 107...
• The farrowing environment is thoroughly contaminated
with PCV2.
• Growing piglets are under constant viral challenge fro...
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...
0
10
20
30
40
50
60
70
80
90
Positive Negative
%PCV2positivepigs
Large Increase in PCR-negative pigs
2006
2012
Change in P...
a b
c d
Anti-Rep
Anti-Cap
Infected + Vaccinated 81%
Vaccinated Only 13%
Background
noise 3%
Negative 3%
Serological Status...
Vaccination Suppresses but does not Cure Infection
Young pigs
(45 kg)
Old pigs
(100 kg)
January neg* neg
March neg neg
May...
Conclusion: PCV2 causes disease, but presence in lymph nodes does not
prevent immune response to PCV2 vaccination.
Kristen...
How is vaccination working????????????
 No one really knows the mechanism.
 Vaccines do not induce robust antibody respo...
Concluding Observations
 PCV2 is a highly conserved virus displaying limited genetic
diversity in the United States
 PCV...
Dr. Michael Murtaugh and Dr. Cheryl Dvorak - Natural Infection, Immunity & Prevalence of PCV2
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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 - Dallas, TX

More presentations at http://www.swinecast.com/2014-boehringer-ingelheim-aasv

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  • 3 over 90% viremic (others 30-50%)know animals supposed to make antibodies to PCV2 around 15 weeks of age and persist long-term. With high levels of viremia wanted to check Ab levels
  • First examined piglets pre-suckling..Unable to correlate piglet viremia with sow parity or sow viremia levels
  • 2 explanations1- non-viremic, but active infection elsewhere (most of non-viremic pigs did have detectible virus in colostrum, oral fluids, or feces)2 – low levels of infection that are below the threshold of detection of the assay
  • Have high serum Ab and extremely high colostrum Ab levels, also able to detect Ab in oral fluids.Looked for correlation between viral lvls and Ab, but no correlationDilutions – serum 1:50 serum, Colost 1:5000 IgG, Colost 1:50 IgA, oral fluids 1:3
  • If the majority of sows are PCV2 pos, piglets are infected in utero, and antibodies do not eliminate virus – this suggests that PCV2 is a persitent infection.
  • Data suggests 2nd model is correct. Piglets are born PCV2 pos even though infection not seen until 10-15 wksHowever, we still need to determine if Mat Ab control infection until those Ab decrease and allow viral replication or the other possibility is that Ab clear the original infection and any reinfections, until the antibodies decrease and are no longer effective
  • Dr. Michael Murtaugh and Dr. Cheryl Dvorak - Natural Infection, Immunity & Prevalence of PCV2

    1. 1. Natural Infection, 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. 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 15Series1 1999 2001 2003 2005 2007 2009 2011 2013 NumberofSequences Year of Isolation 490
    3. 3. Swine Finishing Herds in USA (n=187, pigs >20 weeks) Viremia PCV2 >99% of Herds Positive Antibody >99% of Herds Positive Average PCV2 titer >104 copies per ml 0 50 100 Within Herd Prevalence Frequency(NumberofFarms) 0 100 200 300 400 500 600 2 3 4 5 6 7 8 9 PCV2 DNA copies/ml (log ) Frequency(numberofanimals) 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(NumberofFarms) In 2005, there was no PCVAD in the USA Porcine Circovirus in 2006, USA
    4. 4. Porcine Circovirus in 2006 Pre-PCVAD, Pre-Vaccines Swine Finishing Herds in USA (n=187, pigs >20 weeks) Viremia PCV2 >99% of Herds Positive Antibody >99% of Herds Positive Average PCV2 titer >104 copies per ml 0 50 100 Within Herd Prevalence Frequency(NumberofFarms) 0 100 200 300 400 500 600 2 3 4 5 6 7 8 9 PCV2 DNA copies/ml (log10) Frequency(numberofanimals) 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(NumberofFarms) Puvanendiran et al. 2011. Virus Res 157:92-98.
    5. 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. 6. AB B ANumberperbin CT value X=35.3 X=35.9 X=34.4 Level of Viremia is Not Affected by Genotype of Infecting Viruses Infection with PCV2a=PCV2b= PCV2a+2b
    7. 7. • Pigs at finishing are viremic • Antibody is not controlling infection • What is the source of infection? When do Pigs get Infected?
    8. 8. Sows are viremic Virus in Colostrum Virus in Oral fluids Pre-farrowing Sows are Infected and Shed PCV2 No effect of parity
    9. 9. • Serum and swabs were collected pre-suckling • 78% of piglets were born viremic • All PCR-positive samples were PCV2b (n=219) Serum Piglets are born Viremic Skin Swabs
    10. 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 positive even in the absence of observable viremia. Nonviremic Sows Produce Viremic Piglets A Negative PCR Test is not Proof of Negative
    11. 11. Piglet skin qPCR Detects Live, Infectious Virus in Pigs and Environment, Except on Sanitized Surfaces Piglet serumSow Serum Crate Bar
    12. 12. Serum IgG • Anti-PCV2 antibodies are present in serum, colostrum, and oral fluids of sows • Sows from farm 3 and 5 were vaccinated and have universally high antibodies Colostrum IgG Sows have High Levels of anti-PCV2 Antibodies
    13. 13. PCV2 Infection is Persistent • Even in the presence of PCV2-specific antibodies, 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 %PCV2positivepigs Piglet age (weeks) Viral DNA levels Sow Piglets 0 1 2 3 0 5 10 15 20 25 AverageODvalue Piglet age (weeks) IgG Antibody levels Sow Piglets
    14. 14. Persistent infection: Vaccination 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. 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 - Infection can be Lifelong
    16. 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. 17. 0 10 20 30 40 50 60 70 80 90 Positive Negative %PCV2positivepigs Large Increase in PCR-negative pigs 2006 2012 Change in PCR Status 2006 - 2012
    18. 18. a b c d Anti-Rep Anti-Cap Infected + Vaccinated 81% Vaccinated Only 13% Background noise 3% Negative 3% Serological Status of Finishing Pigs - 2012
    19. 19. Vaccination Suppresses but does not Cure Infection 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. 20. Conclusion: PCV2 causes disease, but presence in lymph nodes does not prevent immune response to PCV2 vaccination. Kristensen et al. 2011. Prev Vet Med 98:250. Vaccination Works: Meta-Analysis (66 trials) Vaccines against PCV2 improve growth Vaccines against PCV2 reduce mortality
    21. 21. How is vaccination working????????????  No one really knows the mechanism.  Vaccines do not induce robust antibody response.  Neutralizing antibodies exist but do not eliminate virus.  Cytotoxic T cells not a general feature of protein vaccines.  But, no question that it works.
    22. 22. Concluding Observations  PCV2 is a highly conserved virus displaying limited genetic diversity in the United States  PCV2 is endemic is swine herds; PCV2b is more common than PCV2a.  PCV2 exposure starts at birth; infection can be lifelong.  Vaccination effectively controls PCVAD and reduces infectious pressure, but does not eliminate virus.

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