Natural Infec-On, Immunity & Prevalence of PCV2-140314153142-phpapp02

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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.

490

500

50

11

Year of Isola-on

MN VDL Sequencing
917 Isolates

PCV2a
2001-2013

PCV2b
2003-2013

Canada 1999
China 2003

2012-2013
mPCV2b

13

2013

Series1
7
9

2011

2009

2007

2005

0.5

2003

2001

0.02

1999

Number of Sequences

2006-2013

15

Porcine Circovirus in 2006, USA


An-body
>99% of Herds Posi-ve

80
Frequency (Number of Farms)

100

Viremia
PCV2 >99% of Herds Posi-ve

60

In 2005, there was no PCVAD in the USA

50

40
20

0
0-10

11-20 21-30 31-40 41-50 51-60 61-70 71-80 81-90 91-100


Within Herd Prevalence

Within Herd Prevalence

Average PCV2 -ter >104 copies per ml


Frequency (number of animals)

Frequency (Number of Farms)

Swine Finishing Herds in USA (n=187, pigs >20 weeks)

600
500
400
300
200
100
0

5
6
7
PCV2 DNA copies/ml (log )

Porcine Circovirus in 2006 Pre-PCVAD, Pre-Vaccines

100

Viremia
PCV2 >99% of Herds Posi-ve

An-body
>99% of Herds Posi-ve
80
Frequency (Number of Farms)

Frequency (Number of Farms)

Swine Finishing Herds in USA (n=187, pigs >20 weeks)

50

60
40
20
0
0-10 11-20 21-30 31-40 41-50 51-60 61-70 71-80 81-90 91-100
Within Herd Prevalence

Within Herd Prevalence

Frequency (number of animals)

Average PCV2 -ter >104 copies per ml


600
500
400
300

Puvanendiran et al. 2011.


Virus Res 157:92-98.

200
100
0

4
5
6
7
PCV2 DNA copies/ml (log )

PCV2b in 48% of pigs


: in 2006
PCV2a in 38% of pigs
qPCR
N=1000
39%
386

400
350

PCV2
a

PCV2
b

29%
286

23%

300

233

250
200

9%

150

95

100
50
0

Rowland et al.

PCV2a
A

PCV2b
B

PCV2a+
AB
PCV2b

Negative
-

Level of Viremia is
Not Aected by
Genotype of
Infec-ng Viruses

Infec-on with
PCV2a=PCV2b=
PCV2a+2b

Number per bin

X=35.3

B
X=35.9

AB
X=34.4

CT value

When do Pigs get Infected?


Pigs at nishing are viremic
An-body is not controlling infec-on
What is the source of infec-on?

Pre-farrowing Sows are Infected and Shed PCV2


Sows are viremic

Virus in Colostrum

No effect of parity

Virus in Oral fluids

Piglets are born Viremic


Serum

Skin Swabs

Serum and swabs were collected pre-suckling


78% of piglets were born viremic
All PCR-posi-ve samples were PCV2b (n=219)

Nonviremic Sows Produce Viremic Piglets


PCV2 is present in presuckling 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.

A Nega-ve PCR Test is not Proof of Nega-ve

qPCR Detects Live, Infec-ous Virus in Pigs and


Environment, Except on Sani-zed Surfaces

Sow Serum

Crate Bar

Piglet serum

Piglet skin

Sows have High Levels of an--PCV2 An-bodies


Serum IgG

Colostrum IgG

An--PCV2 an-bodies are present in serum, colostrum, and oral uids of sows
Sows from farm 3 and 5 were vaccinated and have universally high an-bodies

PCV2 Infec-on is Persistent

IgG An-body levels

3
2

Sow
Piglets

1
0
0

10

15

Piglet age (weeks)

20

25

% PCV2 posi-ve pigs

Average OD value

Even in the presence of PCV2-specic an-bodies,


PCV2 viremia is maintained.
Once an animal is infected, it is infected for life.
Viral DNA levels

100
80
60
40

Sow
Piglets

20
0
0

10

15

20

Piglet age (weeks)

25

Persistent infec-on: Vaccina-on Evidence

One batch
not vaccinated

January
March
May
June
August
October
November
January

Young pigs
(45 kg)
neg*
neg
104
neg
neg
neg
neg
neg

Old pigs
(100 kg)
neg
neg
107
neg
neg
neg
neg
neg

Vaccination can suppress viremia to non-detectable levels.


However, virus reappeared when vaccination was stopped.
Vaccination does not cure infection.

Pigs are Infected at Birth - Infec-on can be Lifelong


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.
Maternal Ab
virus
piglet
antibodies
10-15 weeks

Six Years Later: What is the PCV2 Status


1010

Viral copies/ml

109
108
107
106
105
104
103
102

AB

2006
Viral loads are reduced.

2012

AB

Change in PCR Status 2006 - 2012


Large Increase in PCR-nega-ve pigs
90

% PCV2 posi-ve pigs

80
70
60
50

2006

40

2012

30
20
10
0

Posi-ve

Nega-ve

Serological Status of Finishing Pigs - 2012

An--Rep

Infected + Vaccinated 81%

Background
noise 3%

a" " b"


c" " d"
Nega-ve 3%

Vaccinated Only 13%

An--Cap

Vaccina-on Suppresses but does not Cure Infec-on

One batch
not vaccinated

January
March
May
June
August
October
November
January

Young pigs
(45 kg)
neg*
neg
104
neg
neg
neg
neg
neg

Old pigs
(100 kg)
neg
neg
107
neg
neg
neg
neg
neg

Vaccination can suppress viremia to non-detectable levels.


However, virus reappeared when vaccination was stopped.

Vaccina-on Works: Meta-Analysis (66 trials)


Vaccines against PCV2 improve growth

Vaccines against PCV2 reduce mortality

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.

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.

Concluding Observa-ons
vPCV2 is a highly conserved virus displaying limited gene-c
diversity in the United States
vPCV2 is endemic is swine herds; PCV2b is more common
than PCV2a.
vPCV2 exposure starts at birth; infec-on can be lifelong.

vVaccina-on eec-vely controls PCVAD and reduces
infec-ous pressure, but does not eliminate virus.

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