PCV2: Diagnostics, Control, Protection, and Efficacy Measures

Brian Payne, DVMBoehringer Ingelheim Vetmedica, Inc, St. Joseph, MO, USA

Crash course into PCV2

• PCV2 timeline

• Case load over time

• Diagnostics

• Duration of immunity

• Cross-protection and Mutations

• Vaccine measurements

40 years of PCV2 (select events)

•PCV2 discovered in kidney cell (PK15) line (1974, Tischer)

•PCV and congenital tremors (1994, Hines and Lukert)

•PCV and PMWS linked (1997, Clark)

• First PCV pathogenesis study (1986, Tischer)

•Etiologic agent and PMWS described (1998, Allan, Ellis, Meehan)

FLEXcombo®

3FLEX®

*FLEXcombo’s predecessor was Ingelvac CircoFLEX® – MycoFLEX®

CircoFLEX®

MycoFLEX®

•Classification of PCV1 and PCV2 (1998, Meehan)

Clusters PCV2a, PCV2b nomenclature (2007-8, Olvera, Segalés) ●

PCVAD described (2007, Opriessnig) ●

•PDNS described (2001, Choi)

12-59% morbidity rates in unvaccinated (04-07, USDA)●

Horizontal transmission described (03-11 multiple authors) ●

•Vertical transmission described (99-00, multiple authors)

Global shift from PCV2aPCV2b described (07-08 multiple authors) ●

PCV2 vaccines in N. America (2006) ●

First PCV2 vaccine launched in EU (2004, Reynaud) ●

AASV taskforce (06-09) ●

20141974 1994 20041984 1999 2009

PCV2 clinical sign nomenclature (2012, Segalés) ●

•Serology survey throughout the globe (1982-95, Tischer, Dulac, Harding, Clark, Horner, Edwards, Hines)

PCV2 Cases overtime – Iowa State U.

Opriessnig, 2007, J Vet Diagn invest

Overall trend of porcine circovirus type 2–associated disease (PCVAD) cases submitted to the Veterinary DiagnosticLaboratory at Iowa State University.

PCV2 Cases overtime – Iowa State U.

Opriessnig, 2011, Animal Health Research Reviews

# cases

Madson, ISU-VDL, January 2014

Routine Diagnostics

SerumTissuesPUCS

Oral fluidsEnvironmental

PCR

ELISASequencing

Nucleotide Substitution per 100 residues 0

7.1

2 4 6

13-49311-14 (BIVI 129804) 13-49311-23 (BIVI 129804)

13-49313-12 (BIVI 131678) 13-49314-504 (BIVI 131263)

13-49314-506 (BIVI 131263) 13-49317-426 (BIVI 130279)

HistopathologyIHC

Updated PCV2 qPCR

Chittick, Leman 2013

420

148

PVC2 qPCRs positives4 recent trials

2-4 logs>4 logs

Ingelvac CircoFLEX® PCV2 protection

Parma Ham Studies

Terreni, ESPHM 2009a Terreni, ESPHM 2009b Persico, ESPHM 2013

285 days on feedCircoFLEX®

303 days on feedCircoFLEX®

265 days on feedFLEXcombo®

http://www.epicurus.com

Iberian Ham Studies

Palomo, IPVS 2012 Criado, Emerging & Remerging Diseases, 2011

10 months oldFLEXcombo®

10 months of ageFLEXcombo®

http://www.ibergour.co.uk/

US Field Studies

3 replicates2,338 pigs

d0-first cut d0-second cut d0-final cut 1.45

1.50

1.55

1.60

1.65

1.70

1.75

ADG – competitive PCV2/M. hyo vaccine study

FLEXcombo® Circumvent PCVM®

AD

G, p

ound

s, lb

s

a

a

ab

b

b

ab Means differ (Tukey’s HSD P≤0.05)

BIVI 2011093; Payne IPVS 2012

100% of the pigs,measured all the way to market1 35 70 105 139

0

10

20

30

40

50

60

70

80

90

100

PCV2 qPCR % Positive

Day of Trial

PCV2

QPC

R Pe

rcen

t >4L

ogs

Yes, PCV2 mutants exist

Takahagi, Differential Effects of Porcine Circovirus Type 2 (PCV2) Vaccination on PCV2 Genotypes at Japanese Pig Farms, Virology, 2009, 35-41.

Opriessnig, Halbur, ISU Dz Conf, 2013, p30-34.

CircoFLEX® cross-protection papers• Licensing Data*

• Takahagi, 2009, 16 strains cross-protection paper

• Derosiers, JSHAP, 2009

• Cline, Vet Record, 2008

• Haiwick, AASV, 2014

• Werling, AASV, 2014

*BIVI 6131-0981-04P-036

CircoFLEX® Cross-protection papers

Takahagi, Differential Effects of Porcine Circovirus Type 2 (PCV2) Vaccination on PCV2 Genotypes at Japanese Pig Farms, Virology, 2009, 35-41.

Viremia reduced in all cases

Haiwick, AASV 2014 Oral Presentation

Note: No statistics were conducted on this data

Werling, 2014 AASV, poster

• Designed to evaluate CMI

* = p<0.05; ** = p,0.01; *** = p<0.001

** *

***

***

** *

Novel mutations of PCV2

Novel (2012) PCV2b described by Dr. Opriessnig

Xiao, Opriessnig, JVI, 2012

Opriessnig, AASV, 2012

Opriessnig, Vet Micro 2012 paper

ISU diagnostic reports

PCV2a PCV2b “mPCV2b”

ORF 1 PCR + + +

ORF 2 a/b differential

+ (a) + (b) +(b) / -

# nucleotides 702 702 705

# amino acids 233 233 234

Comparison between PCV2 strains

Opriessnig, Halbur, ISU Dz Conf, 2013, p30-34

• ORF 2 homology to:• PCV2a: 90.6-91.0%• PCV2b: 93.6-94.9%

• ORF1 homology to:• PCV2a: 99.0-99.4%• PCV2b: 98.7%

Measurements

• Clinical picture• Diagnostics• Performance

Pre-PCV2 vaccines

• Prior to commercially available PCV2 vaccines, several PCV2 studies demonstrated that levels of PCV2 virus in the serum (viremia) and tissues were correlated to the severity of disease1-12

• Clinically ill pigs had higher viremia and PCV2 tissue levels than subclinical pigs

• In these non-vaccinated pigs, lesions correlated with viral load

• Suggestions that 107 viral load could be used to diagnose PMWS1-3

PCV2 vaccines enter the market

• In vaccinated pigs high levels of viremia are rarely seen13

• All commercial vaccines reduce viremia16,17

• In vaccinated pigs, viremia is not predictive to production performance• North American14 and European15 studies

• Different PCV2 protocols (1 vs. 2 dose) show no difference in magnitude of viremia13

• Elimination of PCV2 with vaccine has NOT been demonstrated

Holck, Leman 2009 Maass, Leman 2009

Viremia and ADG – no correlation

Percentage of pigs positive, PCV2 qPCR

TRIA

L A

TRIA

L B

3 10 13 16 19 220%

10%20%30%40%50%60%70%80%90%

100%

NVCFLEXPCV M

Weeks of Age

3 7 10 14 19 230%

20%

40%

60%

80%

NVCCircoFLEXFostera

Bretey et al. 2013. Leman Conference

nStart

Avg. wt Start

Tot WtStart, lbs

nEnd

Avg. wtEnd, lbs

Total WtEnd, lbs

Avg. wt Gain, lbs

CircoFLEX®

Fostera® PCV

CircoFLEX®

Fostera® PCV

CircoFLEX®

Fostera® PCV

nStart

444 444 145 150 433 431

Avg. wt Start

13.98 14.12 14.19 14.22 18.75 18.64

Tot WtStart, lbs

6,207.12 6,269.28 2,057.99 2,133.45 8,118.75 8,033.84

nEnd

425 421 144 149 413 410

Avg. wtEnd, lbs

243.60 242.19 260.21 256.51 237.72 236.28

Total WtEnd, lbs

103,530 101,962 37,470.2 38,220.0 98,178.4 96,874.8

Avg. wt Gain, lbs

229.62 228.07 246.021 242.288 218.97 217.64

CircoFLEX®

Fostera® PCV

1,022 1,025

16.03 16.03

16,383.9 16,436.6

982 980

243.61 241.99

239,178.6 237,056.8

227.58 225.96

3 Trial Results

↓3 pigs

Equal

↑2 pigs

↑1.62 lbs

↓52.70 lbs

↑2,121.8 lbs

↑1.62 lbs

Trial 1* Trial 2* Trial 3* Combined

Note that these are numerical differences; *BIVI2011191; BIVI2012056; BIVI2011252

Example scenario financialsCircoFLEX® Vaccine B

Number of pigs started 1,000 1,000

Starting Weight 16.0 lbs

Mortality percent 3.9% 4.4%

Total pigs marketed 961 956

Days on Feed 140 days

ADG, lbs 1.63 1.62

Average live weight per pig, lbs 244.2 lbs 242.8 lbs

Carcass yield estimate 74%

Estimated carcass weight 180.7 179.7

Total wt. of carcasses sold 173,653 lbs 171,793 lbs

Difference in lbs, kg 1,860 lbs = 844 kg

Carcass price , Dec 2013* $0.76 / lb

Diff. in total carcass price $1,414

Total carcass price/1,000 pigs $1.41/pig benefit CircoFLEX® over Vaccine B* http://www.agmanager.info/livestock/marketing/graphs

FLEX FamilyCustomized Control

because every herd is unique