Dr. Mike Roof - Impact of Porcine Reproductive & Respiratory Syndrome (PRRS) vaccination on infectious load and implications for area control and eradication
1) A study examined the impact of vaccination with Ingelvac PRRS MLV on pigs challenged with varying doses of wild-type PRRSV.
2) The results showed that vaccination mitigated the consequences of infection at all challenge doses, as vaccinated pigs had reduced viremia, fewer days of fever, and higher average daily weight gain compared to non-vaccinated pigs.
3) At challenge doses of 2 logs or less, vaccinated pigs performed similarly to non-challenged pigs, suggesting vaccination prevented clinical consequences of infection at low exposure levels.
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Similaire à Dr. Mike Roof - Impact of Porcine Reproductive & Respiratory Syndrome (PRRS) vaccination on infectious load and implications for area control and eradication (20)
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Dr. Mike Roof - Impact of Porcine Reproductive & Respiratory Syndrome (PRRS) vaccination on infectious load and implications for area control and eradication
1. Mike Roof, PhD
Executive Director Bio R&D
Impact of PRRS vaccination on
infectious load and implications
for area control
4. • 2100 PRRS negative weaned pigs
• 42 pens / room with 25 pigs/pen ≈ 1050 pigs/room
• Divided by a wall with separated pits & attic
•Biosecure entry system implemented for each room
Non-vaccinated control
Room (North)
MLV vaccinated
Room (South)
Shower
& office
Loading chute
•Objective of study was to quantify the effect of MLV vaccine on
performance and measure wild-type virus (WTV) shedding in pigs
vaccinated at weaning and challenged 4 weeks later.
S Dee, J Nerem,T Wetzell, J P Cano, and J Rustvold
5. Study design
MLV
NVC
-1 0 3 7 14 21 29 32 36 43 52 58 66 80 93 122 147 DPV
Arrival
Sorting
Weigh
ID
Ingelvac® PRRS
MLV
PRRSv IM
inoculation 10%
of pigs
» Serum (30 per room) & OF (6 per room) PCR & ELISA
» 20-30’ bioaerosol 6 days / week at 8AM (Liquid cyclonic collector ®)
8. Control
Group
Vaccine
Group
DD
DD
-29 5 0 3 8 36 70 95 118 DPI
Pig arrival
Sorting Weigh
ID
1-18-2
challenge
ATP vaccinations
» Serum and Bioaerosol samples tested by RT-PCR
Slaughter
Weigh
9. Therapeutic administration of Ingelvac PRRS® reduced PRRSV
shedding in aerosol
PRRSV in aerosol CONTROL VACCINATED
Mean (RNA copies/mL) 4.3 x 108 a 4.5 x 108 a
95% conf interval 2.6 x108 - 6.1 x 108 a 2.7 x 108 - 8.1 x 108 a
# pos days 31a 17b
last DPI positive 70 45
# pos days (McNemar's test p-value 0.0004)
(Linhares et al., 2012)
10. Role of Vaccine for PRRS Control
Direct benefit – proven reduced clinical disease following wild type
exposure in heterologous challenge studies
– Pig model - % lung lesions
– Sow Model – reproductive performance
Indirect benefit - Reduction of wt-virus shedding
Maintain uniform immunity
– Within and between populations
– Reduce level of virus
• Direct and Indirect benefit-mitigate consequences of infection
improving health and performance
• Vaccine Derived Immunity Matters
11. Role of Vaccine - Unanswered Questions
What is the effect of challenge dose in vaccinated pigs?
1. What challenge dose of virulent PRRSV is required to
cause infection and consequences of infection in a
vaccinated animal?
– viremia, fever, reduced ADWG
– How does vaccination impact the host PRRS status to various dose exposures?
2. Is there a challenge dose where vaccination prevents
consequences of infection?
– Does vaccine “blunt” or “shield” a pig from PRRS infection at any level?
– Aerosols, fomites, and transmission with lower levels of PRRS exposure (vs pig to pig)
– Applications to regional control programs
12. Study Design
Randomized, blinded vaccination-challenge study
Pigs used for the study were 3 wks of age and PRRSV naïve;
confirmed PCR negative for PRRSV
Statistics
• Results summarized via descriptive statistics by day,
challenge dose and group
• For number days pyrexic and ADWG post-challenge
• P-value < 0.05 was used to indicate statistical significance
13. Study Design
Group
No. Inglevac
PRRS® MLV
Vaccinated
Pigs
(2ml IM)
No. Non-
vaccinated
Challenge
Control
Pigs
PRRSV
SDSU-73
Challenge
Dosage
(Log10TCID5
0/ml)
(2ml IN)
Study
Termination
Day 0 Day 0 Day 28 Day 70
1 10 10 4 logs
2 10 10 3 logs
3 10 10 2 logs
4 10 10 1 log
5 10 - None
14. Study Design
Parameter Day
Viremia PCR (+/-) 0, 7,14, 21, 28, 31, 33, 35, 38, 42,
and weekly thereafter until day 70
Temperature
(Pyrexia defined as a rectal temp
> 40.0°C)
Day 27
Daily for 14 days until Day 42
ADWG 0, 28, 70
15. Results – Interpretation and Considerations
• Viremia is measured by PCR which was the most conservative evaluation and
measure of vaccination impact.
• At high CT values that are PCR positive, we expect many of these samples
would be virus isolation negative or very low levels of virus
• Current PCR results did not differentiate between Ingelvac and SDSU 73 and
so data needs assessed by GROUP comparison of Ingelvac only vs
Vacc/Exposed.
• Future opportunities that are being considered
• Complete virus isolation
• Assess via differential PCR
Company Presentation 2013 Boehringer Ingelheim Animal Health 15
16. Results – Viremia 4log challenge
0%
20%
40%
60%
80%
100%
120%
28 31 33 35 38 42 49 56 63 70
%PCRPositive
Days
Ingelvac
PRRS® MLV
(challenge)
Challenge
Control (non-
vaccinated)
Ingelvac
PRRS® MLV
(no challenge)
Figure 1. Percentage of viremic pigs per treatment group challenged with 4 logs
Reduction in post-
challenge viremia
in vaccinates
17. Results – Viremia 2log challenge
Figure 2. Percentage of viremic pigs per treatment group challenged with 2 logs
0%
20%
40%
60%
80%
100%
120%
28 31 33 35 38 42 49 56 63 70
%PCRPositive
Days
Ingelvac
PRRS® MLV
(challenge)
Challenge
Control (non-
vaccinated)
Ingelvac
PRRS® MLV
(no challenge)
Vaccinates
similar to non-
challenged pigs
18. Results – Viremia following 2 log virus challenge
Average CTValues per Group Challenged w/ 2 Logs of Virus
19. Results – Pyrexia/Fever (40 C)
Mean Number Days Pyrexic Post-Challenge
Treatment Group
4 log
challenge
3 log
challenge
2 log
challenge
1 log
challenge
No
challenge
Ingelvac PRRS® MLV 4.41 4.21 1.01 1.41 1.8
ChallengeControl
(non-vaccinated)
11.2 8.8 10.0 6.0 -
Vaccinated groups had significant decrease in
fever days and maintained lower average
temperature at all challenge doses
Vaccinates not
different than
non-challenge
1 Statistically significant difference (P<0.05) in ADWG between Ingelvac PRRS®MLV and Challenge control groups based on model prediction
Measurable negative impact in non-
vaccinated challenged groups at all
challenge doses
20. Results – Average Daily Weight Gain
ADWG (lbs) Days 28-70
Treatment Group
4 log
challenge
3 log
challenge
2 log
challenge
1 log
challenge
No challenge
Ingelvac PRRS®
MLV
1.41 1.291 1.701 1.641 1.67
ChallengeControl
(non-vaccinated)
1.18 1.06 1.15 1.23 -
1 Statistically significant difference (P<0.05) in ADWG between Ingelvac PRRS®MLV and Challenge control groups based on model prediction
Vaccinated groups higher ADWG compared to
non-vaccinated at all challenge doses
Measurable negative
impact in non-vaccinated
groups at all challenge
doses
Vaccinates
not different
than non-
challenge
21. Role of Vaccine - Questions
Is there a challenge dose where vaccination prevents
consequences of infection?
At a challenge of 2 logs or less, the consequences of challenge in
vaccinated pigs were similar to non-challenged pigs
At all challenge doses, Ingelvac® PRRS MLV mitigated the
consequences of infection as compared to challenge controls using
the SDSU 73 wt virus
ADWG Viremia Temperature
↑ ↓ ↓
22. Take Home Messages
Relevance in the field
For pigs or populations of pigs at risk of challenge/infection Ingelvac PRRS® MLV derived
immunity matters!
- Direct benefit – Reduced clinical impact in vaccinated pigs following wt exposure
- Indirect benefit
- Reduced viral load in pig and viral shedding (including aerosol)
- “blunting” of low level exposure to further reduce risk
- May be important in area control programs
Maintaining uniform immunity within and between populations can reduce level of virus
- Farm and flow, system-based, or ARC should continue a focused PRRS control programs
utilizing vaccine.
- Don’t let your foot off the gas!
- Beat virus down to a level of little consequence
23. Take Home Messages
Relevance in the field
At lower levels of challenge the consequences in vaccinated
pigs were similar to non-challenged pigs
At any level of challenge, Ingelvac PRRS MLV demonstrated
increase in ADWG and a decrease in temperature and viremia as
compared to the challenge controls
At any level of challenge the impact in non-vaccinated (non-
immune) pigs is significant as measured by ADWG, viremia.
1.
2.
3.
24. Narrowing the Funnel – incremental advances in PRRS
control moving toward area control
PRRS “Cloud”
Immunity to Reduce Clinical
Disease
Immunity/Management to
Reduce PRRS Load
Pig Resistance to PRRS
- Pig Genetics
-Reduce host infection
(Immune)
- Area Control and reduced
exposure
Company Presentation 2013 Boehringer Ingelheim Animal Health 24
25. Next Level of Questions and Challenges
• Impact of the challenge virus used and impact on the results!!?
• VR2332 vs MN184 vs SDSU 73 vs 1-18-4……
• Study used Neg pigs:
• Would the use of previously exposed animals that were then vaccinated have
an impact?
• Would pigs vaccinated multiple times have different results and raised the
dose that could be “blunted”??
• Impact of vaccine timing and animal age!!?
• Is the effect the same in a growing pig vs a sow/gilt?
Company Presentation 2013 Boehringer Ingelheim Animal Health 25
Indirect Benefit-
Demonstrated through
Control and field based studies
ARC projects
Maintain uniform immunity
Within and between populations
Reduce level of virus
A low level PRRS challenge was no match against a full dose of Ingelvac® PRRS.
Ingelvac® PRRS vaccine-derived immunity prevented the consequences of infection
Is difference in temperature vaccinates vs challenge control statistically significant?
If pigs are at any risk to PRRS infection, Immunity Matters
This is super-cool …….. At any level of challenge there is an impact in non-vaccinated challenge controls. Ingelvac MLV demonstrates mitigation of challenge impact at 3 and 4 log challenge ……. Assume statistically significant? At 4 log challenge level w/ inclusion of Prime Pac vaccinated group ……. Prime Pac group not different than challenge controls and assume improved ADWG in Ingelvac group is statistically significant. At challenge level 2 logs or less ……. Ingelvac vaccinated group not different from vaccinated-non-challenged group ……. No impact from challenge and prevention of infection or impact of infection as measured by ADWG ….. Again, assuming statistical significance?
Full dose Ingelvac® PRRS immunity yields optimal protection and performance against all levels of challenge
This study has relevance in the field as implementation of vaccine in a systematic and coordinated methodology in a “system-based” and “area/region-based” program can mitigate the consequences of PRRSV infection – subsequently improving health and performance – and may reduce the level of challenge virus within and between vaccinated populations over-time further limiting the consequences of infection in vaccinated populations
This study has relevance in the field as implementation of vaccine in a systematic and coordinated methodology in a “system-based” and “area/region-based” program can mitigate the consequences of PRRSV infection – subsequently improving health and performance – and may reduce the level of challenge virus within and between vaccinated populations over-time further limiting the consequences of infection in vaccinated populations
This study has relevance in the field as implementation of vaccine in a systematic and coordinated methodology in a “system-based” and “area/region-based” program can mitigate the consequences of PRRSV infection – subsequently improving health and performance – and may reduce the level of challenge virus within and between vaccinated populations over-time further limiting the consequences of infection in vaccinated populations