PCV2 is highly prevalent in swine herds worldwide. The document summarizes research showing that: 1) Pigs are born already infected with PCV2, as the virus is present in pre-farrowing sows and transmitted to piglets in utero or during birth. 2) Piglets remain viremic for life even in the presence of antibodies, as PCV2 infection causes lifelong persistent infection. 3) The farrowing environment is thoroughly contaminated with PCV2, exposing growing piglets to constant viral challenge from the sow and environment.

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.