dr. brian payne - pcv2 vaccine cross-protection: identification of sequences in successfully...

PCV2 vaccine cross-protection: Identification of sequences in successfully vaccinated field casesBrian Payne1, DVM; Amy Jacobs2, BS; Cheryl Dvorak3, PhD; Michael Murtaugh3, PhD1Boehringer Ingelheim Vetmedica, Inc. (BIVI), St. Joseph, Missouri 2Field Research Services, Boehringer Ingelheim Vetmedica, Inc., Ames, Iowa3 Department of Veterinary and Biomedical Sciences, U. of MN, St. Paul, Minnesota

Summary• Mutations in PCV2 do occur• Evolution of the virus is inevitable

• CircoFLEX® continues to protect• On-going monitoring is

recommended• Root cause analysis needed

Yes, mutants exist• Commercial PCV2

vaccines are based on PCV2a

• PCV2b became dominant strain when PCV2 vaccines were launched

• PCV2d has emerged and is becoming predominant strain

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

PCV2 compilation, NAHMS 2012• More mixing of A and

B compared to 2006• 82% had PCV2b• 48% had PCV2a• 35% mixed infections

University SubmissionsNumber of sequences, n

PCV2a PCV2bmPCV2b =

PCV2dGrand Total

2013 10 30 18 582014 5 11 37 532015 26 13 136 175Grand Total 41 54 191 286

VDL ALL VDL (no BI) BI only

PCV2a 14 7 7PCV2b 27 7 20PCV2d 47 14 33PCV2e 3 1 2

U of MNVDL2015

ISUVDL

ISU Submissions, over time

2013 2014 20150

20406080

100120140160

PCV2a PCV2b PCV2d

Num

ber o

f Seq

uenc

es, n

Data Courtesy of Kent Schwartz (ISU)

University Submissions, 2015

2613

136

2015 ISU Sequences, n

PCV2a PCV2b PCV2d

7

714

1

2015 U of MN Sequences, n

PCV2a PCV2b PCV2d PCV2e

We need to monitor overall trends• Cases = Disease present• Diagnostic acquisitions

• Controls = No disease• Rarely submitted in PCVAD cases• NAHMS studies are beneficial• Intentional control case studies such as this

one can aid in the understanding of root cause

Primary Objective• Identify PCV2 isolates in herds where:• nursery and finisher production

performance was meeting the systems’ expectations

• no clinical PCVAD signs were apparent • Prior to and individual groups sampled

• both the ownership and veterinary staff were satisfied

• using Ingelvac CircoFLEX® at weaning age

SamplingSerum: • 432 samples; 23

farmsOral fluids: • 168 samples; 24

farmsLung homogenate:• 1 farm from 5 pigs

Laboratories for PCV2 PCR:• Health Management

Center (HMC)• Serum and Oral

Fluids• Iowa State VDL• Lung

Homogenate

48farms

Herd Level Results• Similar to previous

surveys conducted, irrespective of vaccine protocol used

• Does not mean diseaseIndicates PCV2 exposure

27 / 48(+) PCV2

PCR

Results, Sample Level  Serum Oral FluidNo. samples tested, total 432 168No. and Percent Positive PCR, % 50/432 11.6% 67/168 39.9%Sequencing Success 

Cq<30 14/14 100% 13/13 100%Cq 30-32 7/7 100% 3/4 75%

Cq>32 0/3 0% 0/00%

Cq = Cycle of quantification; traditionally reported as Ct value

Geography of successful sequences

Bioportal (University of California, Davis) map

Sequences

3

21

16

Number of Sequences, n

PCV2a PCV2b PCV2d

PCV2 Linear Dendrogram

Bioportal (University of California, Davis) PCV2 traditional linear dendrogram rooted to PCV2 Reference sequence JF290418

Megasoftware (Tempe, AZ) Compared amongst U of MN VDL submissions since 2005 (n>700 sequences)

PCV2 radial dendrogram

CircoFLEX® cross-protection papers

Paper Field Strain(s) Challenging Pigs

Licensing Data* Heterologous PCV2aTakahagi, Virology, 2009 16 heterologous strains (Asia)

6 heterologous PCV2a-14 heterologous PCV2a-26 heterologous PCV2b

Derosiers, JSHAP, 2009 Heterologous PCV2b (Canada)Cline, Vet Record, 2008 Heterologous PCV2b

Roof, Leman, 2010 Heterologous PCV2b (China)Eichmeyer, in review, 2015# Heterologous PCV2b

Haiwick, AASV, 2014 Heterologous PCV2bWerling, AASV, 2014 Heterologous PCV2b

Opriessnig, Vaccine, 2014 Heterologous PCV2d**Jeong, Vet Micro, 2015 Heterologous PCV2d**

*BIVI 6131-0981-04P-036; #, BIVI 2014165; ** mPCV2b reclassified to PCV2d

So why do we still get cases of PCVAD

Summary• PCV2 can be found in successfully

vaccinated populations• PCV2 is ubiquitous and vaccination is needed

• PCV2b and PCV2d make up the vast majority of the sequences in the industry• Both in control study and diagnostic labs

• Sequencing is highly successful of PCV2 at Cq values ≤ 32

Summary• Individual publications based on field

data have demonstrated that Ingelvac CircoFLEX® can help protect pigs exposed to PCV2a, PCV2b and PCV2d

• Continual PCV2 mutations will occur• Monitoring is important• Root cause analysis is an important

step in the practical assessment of PCVAD

Gratitude• Multiple practitioners, producers, technical

service personnel, interns and farm staff for the collection of the samples

• BIVI veterinarians, sales representatives, field research leaders for the coordination, collection of samples

• BIVI HMC diagnostic lab for sample coordination

• Murtaugh/Dvorak lab and Amy Jacobs for coordination of the results and interpretation

• Hayley Oswald and Eduardo Fano