Dr. Brian Payne - PCV2: Diagnostics, Control, Protection, and Efficacy Measures

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Information about Dr. Brian Payne - PCV2: Diagnostics, Control, Protection, and Efficacy...

Published on March 14, 2014

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PCV2: Diagnostics, Control, Protection, and Efficacy Measures - Dr. Brian Payne, Boehringer Ingelheim Vetmedica, Inc, from the Boehringer Ingelheim Pre-AASV Conference, February 28, 2014 - Dallas, TX

More presentations at http://www.swinecast.com/2014-boehringer-ingelheim-aasv

PCV2: Diagnostics, Control, Protection, and Efficacy Measures Brian Payne, DVM Boehringer 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 PCV2aPCV2b 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 Diagnostic Laboratory at Iowa State University.

PCV2 Cases overtime – Iowa State U. Opriessnig, 2011, Animal Health Research Reviews # cases Madson, ISU-VDL, January 2014

Routine Diagnostics Serum Tissues PUCS Oral fluids Environmental PCR ELISA Sequencing Nucleotide Substitution per 100 residues 0 7.1 246 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) Histopathology IHC

Updated PCV2 qPCR Chittick, Leman 2013 420 148 PVC2 qPCRs positives 4 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 feed CircoFLEX® 303 days on feed CircoFLEX® 265 days on feed FLEXcombo® http://www.epicurus.com

Iberian Ham Studies Palomo, IPVS 2012 Criado, Emerging & Remerging Diseases, 2011 10 months old FLEXcombo® 10 months of age FLEXcombo® http://www.ibergour.co.uk/

US Field Studies 3 replicates 2,338 pigs 1.45 1.50 1.55 1.60 1.65 1.70 1.75 d0-first cut d0-second cut d0-final cut ADG,pounds,lbs ADG – competitive PCV2/M. hyo vaccine study FLEXcombo® Circumvent PCVM® 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 market 0 10 20 30 40 50 60 70 80 90 100 1 35 70 105 139 PCV2QPCRPercent>4Logs Day of Trial PCV2 qPCR % Positive

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 TRIALATRIALB 0% 20% 40% 60% 80% 100% 3 10 13 16 19 22 Weeks of Age NVC FLEX PCV M 0% 20% 40% 60% 80% 3 7 10 14 19 23 NVC CircoFLEX Fostera Bretey et al. 2013. Leman Conference

n Start Avg. wt Start Tot Wt Start, lbs n End Avg. wt End, lbs Total Wt End, lbs Avg. wt Gain, lbs Circo FLEX® Fostera® PCV Circo FLEX® Fostera® PCV Circo FLEX® Fostera® PCV n Start 444 444 145 150 433 431 Avg. wt Start 13.98 14.12 14.19 14.22 18.75 18.64 Tot Wt Start, lbs 6,207.12 6,269.28 2,057.99 2,133.45 8,118.75 8,033.84 n End 425 421 144 149 413 410 Avg. wt End, lbs 243.60 242.19 260.21 256.51 237.72 236.28 Total Wt End, 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 Circo FLEX® 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 Notethatthesearenumericaldifferences;*BIVI2011191; BIVI2012056; BIVI2011252

Example scenario financials CircoFLEX® 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 Family Customized Control because every herd is unique

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