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