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.

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

Num

ber o

f Seq

uences

Year of Isola-on

490

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

Freq

uency (Num

ber o

f Farms)

0

100

200

300

400

500

600

2 3 4 5 6 7 8 9 PCV2 DNA copies/ml (log10)

Freq

uency (num

ber o

f 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

Freq

uency (Num

ber o

f Farms)

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)

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

Freq

uency (Num

ber o

f Farms)

0

100

200

300

400

500

600

2 3 4 5 6 7 8 9 PCV2 DNA copies/ml (log10)

Freq

uency (num

ber o

f 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

Freq

uency (Num

ber o

f Farms)

Puvanendiran et al. 2011. Virus Res 157:92-98.

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

PCV2a

PCV2b

qPCR

Rowland et al.

AB

B

A Num

ber p

er bin

CT value

X=35.3

X=35.9

X=34.4

Level of Viremia is Not Aected by Genotype of

Infec-ng Viruses

Infec-on with PCV2a=PCV2b=

PCV2a+2b

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

When do Pigs get Infected?

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-posi-ve samples were PCV2b (n=219)

Serum

Piglets are born Viremic

Skin Swabs

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

Piglet skin

qPCR Detects Live, Infec-ous Virus in Pigs and Environment, Except on Sani-zed Surfaces

Piglet serum Sow Serum

Crate Bar

Serum 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

Colostrum IgG

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

PCV2 Infec-on is Persistent

Even in the presence of PCV2-specic 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 % PCV

2 po

si-v

e 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

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.

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

Six Years Later: What is the PCV2 Status

A B AB A B AB102103104105106107108109

1010

Vira

l cop

ies/

ml

2006 2012

Viral loads are reduced.

0

10

20

30

40

50

60

70

80

90

Posi-ve Nega-ve

% PCV

2 po

si-v

e pigs

Large Increase in PCR-nega-ve pigs

2006

2012

Change in PCR Status 2006 - 2012

a" " b"c" " d"

An--Re

p

An--Cap

Infected + Vaccinated 81%

Vaccinated Only 13%

Background noise 3%

Nega-ve 3%

Serological Status of Finishing Pigs - 2012

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.

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

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.