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.
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
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
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.
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.
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
• Pigs at finishing are viremic• Antibody is not controlling infection• What is the source of infection?
When do Pigs get Infected?
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
• 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
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
Piglet skin
qPCR Detects Live, Infectious Virus in Pigs and Environment, Except on Sanitized Surfaces
Piglet serumSow Serum
Crate Bar
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
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
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.
• 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
Six Years Later: What is the PCV2 Status
Viral loads are reduced.
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
Anti-
Rep
Anti-Cap
Infected + Vaccinated 81%
Vaccinated Only 13%
Background noise 3%
Negative 3%
Serological Status of Finishing Pigs - 2012
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.
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
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.
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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