Natural Infec-on, Immunity & Prevalence of PCV2-140314153142-phpapp02
Dr. Michael Murtaugh and Dr. Cheryl Dvorak - Natural Infection, Immunity & Prevalence of PCV2
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Transcript of Dr. Michael Murtaugh and Dr. Cheryl Dvorak - Natural Infection, Immunity & Prevalence of PCV2
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Natural Infection, Immunity & Prevalence of PCV2Michael Murtaugh and Cheryl Dvorak
University of Minnesota, USA
AcknowledgementsCharles Haley and Eric Bush, USDA-APHISSuresh Tikoo, VIDO
SponsorsUniversity of Minnesota SDECBoehringer Ingelheim Vetmedica, Inc.
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Canada 1999mPCV2b
PCV2a2001-2013
PCV2b2003-2013
2006-2013
China 2003
2012-2013
MN VDL Sequencing917 Isolates
1 2 3 4 5 6 7 8 9 10 11 12 13 14 150.5
5
50
500
Series11999
2001
2003
2005
2007
2009
2011
2013
Num
ber o
f Seq
uenc
es
Year of Isolation
490
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Swine Finishing Herds in USA (n=187, pigs >20 weeks)
ViremiaPCV2 >99% of Herds Positive
Antibody>99% of Herds Positive
Average PCV2 titer >104 copies per ml
0
50
100
0-1011-20
21-3031-40
41-5051-60
61-7071-80
81-90
91-100
Within Herd Prevalence
Freq
uenc
y (N
umbe
r of F
arm
s)
0
100
200
300
400
500
600
2 3 4 5 6 7 8 9PCV2 DNA copies/ml (log10)
Freq
uenc
y (n
umbe
r of a
nim
als)
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
Freq
uenc
y (N
umbe
r of F
arm
s)
In 2005, there was no PCVAD in the USA
Porcine Circovirus in 2006, USA
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Porcine Circovirus in 2006 Pre-PCVAD, Pre-Vaccines
Swine Finishing Herds in USA (n=187, pigs >20 weeks)
ViremiaPCV2 >99% of Herds Positive
Antibody>99% of Herds Positive
Average PCV2 titer >104 copies per ml
0
50
100
0-1011-20
21-3031-40
41-5051-60
61-7071-80
81-90
91-100
Within Herd Prevalence
Freq
uenc
y (N
umbe
r of F
arm
s)
0
100
200
300
400
500
600
2 3 4 5 6 7 8 9PCV2 DNA copies/ml (log10)
Freq
uenc
y (n
umbe
r of a
nim
als)
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
Freq
uenc
y (N
umbe
r of F
arm
s)
Puvanendiran et al. 2011. Virus Res 157:92-98.
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A B AB -0
50
100
150
200
250
300
350
400
286
386
95
233
N=1000
PCV2a PCV2b PCV2a+PCV2b
Negative
29%
39%
9%
23%
PCV2b in 48% of pigsPCV2a in 38% of pigs : in 2006
PCV2a
PCV2b
qPCR
Rowland et al.
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AB
B
AN
umbe
r per
bin
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
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• Pigs at finishing are viremic• Antibody is not controlling infection• What is the source of infection?
When do Pigs get Infected?
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Sows are viremic
Sows are viremic
Virus in ColostrumVirus in Colostrum Virus in Oral fluidsVirus in Oral fluids
Pre-farrowing Sows are Infected and Shed PCV2
No effect of parity
No effect of parity
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• Serum and swabs were collected pre-suckling• 78% of piglets were born viremic• All PCR-positive samples were PCV2b (n=219)
SerumSerum
Piglets are born Viremic
Skin SwabsSkin Swabs
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PCV2 is present in pre-suckling piglet serum
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
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Piglet skin
qPCR Detects Live, Infectious Virus in Pigs and Environment, Except on Sanitized Surfaces
Piglet serumSow Serum
Crate Bar
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Serum IgGSerum 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 IgGColostrum IgG
Sows have High Levels of anti-PCV2 Antibodies
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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 5 10 15 20 250
20
40
60
80
100Viral DNA levels
SowPiglets
Piglet age (weeks)
% P
CV2
posi
tive
pigs
0 5 10 15 20 250
1
2
3IgG Antibody levels
SowPiglets
Piglet age (weeks)
Ave
rage
OD
val
ue
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Persistent infection: Vaccination Evidence
Young pigs (45 kg)
Old pigs (100 kg)
January neg* negMarch neg negMay 104 107
June neg negAugust neg negOctober neg negNovember neg negJanuary 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.
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• 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
pigletantibodies
10-15 weeks
Pigs are Infected at Birth - Infection can be Lifelong
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Six Years Later: What is the PCV2 Status
Viral loads are reduced.
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Positive Negative0
10
20
30
40
50
60
70
80
90
Large Increase in PCR-negative pigs
20062012
% P
CV2
positi
ve p
igs
Change in PCR Status 2006 - 2012
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Anti-
Rep
Anti-Cap
Infected + Vaccinated 81%
Vaccinated Only 13%
Background noise 3%
Negative 3%
Serological Status of Finishing Pigs - 2012
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Vaccination Suppresses but does not Cure Infection
Young pigs (45 kg)
Old pigs (100 kg)
January neg* negMarch neg negMay 104 107
June neg negAugust neg negOctober neg negNovember neg negJanuary neg neg
One batch not vaccinated
Vaccination can suppress viremia to non-detectable levels. However, virus reappeared when vaccination was stopped.
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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
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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.
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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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