dr. reid philips - comparative efficacy evaluation of two modified-live prrs vaccines
TRANSCRIPT
Evaluation of PRRSV challenge dose in vaccinated pigs
AASV Annual MeetingTechnical Partners Session
February 28th, 2016
Objective of Study· Evaluate the effect of PRRSV challenge dose in Ingelvac PRRS® MLV vaccinated pigs in a respiratory challenge model
Primary Objective: Question?
· In vaccinated pigs1. What challenge dose of virulent PRRSV is
required to cause infection and consequences of infection?
- viremia, fever, reduced ADWG
2. Is there an infectious dose where vaccination prevents consequences of infection?
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
Study Design
Group
No. InglevacPRRS® MLVVaccinated
Pigs(2ml IM)
No. Non-vaccinatedChallenge
ControlPigs
PRRSV SDSU-73
ChallengeDosage
(Log10TCID50/ml)
(2ml IN)
Study
Termination
Day 0 Day 0 Day 28 Day 70
1 10 10 4
2 10 10 3
3 10 10 2
4 10 10 1
5 10 - None
Study Design
Parameter DayViremia 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 27Daily for 14 days until Day 42
ADWG 0, 28, 70
Study Design· Statistics- Results summarized via descriptive statistics by day, challenge dose and group
- For number days pyrexic and ADWG post-challenge- Linear regression model incorporating treatment &
challenge dose- P-value < 0.05 was used to indicate statistical significance
Results – Viremia following 4 log virus challenge· Following challenge, all pigs in Ingelvac PRRS® MLV vaccinated
groups 1 & 2 (4 and 3 log challenge) became viremic by day 31· Following day 42 (14 days post-challenge), viremia begins
decreasing in vaccinates until day 70· From day 42 to day 70, vaccinated pigs in groups 1 & 2 demonstrate
less percent PCR positive pigs than non-vaccinated-challenged pigs- Reduction in post-challenge viremia in vaccinated pigs
28 31 33 35 38 42 49 56 63 700%
20%40%60%80%
100%120%
Ingelvac PRRS® MLV
Challenge Control (non-vaccinated)
Ingelvac PRRS® MLV (no challenge)
Days
% P
CR
Pos
itive
Figure 1: Percentage of viremic pigs per treatment group challenged with 4 logs
Results – Viremia following 2 log virus challenge· At a challenge dose of 2 logs or less (groups 3 & 4)
- Vaccinated pigs demonstrate less percent PCR positive pigs than the non-vaccinated challenge controls
- Pattern of viremia following challenge is similar to vaccinated non-challenged pigs- Consequences of challenge in vaccinates similar to non-challenged pigs
· As challenge dose decreases, the percentage of viremic pigs in vaccinated groups decreases
· At all challenge doses, the non-vaccinated and challenged pigs show similar post-challenge viremia profile
28 31 33 35 38 42 49 56 63 700%
20%40%60%80%
100%120%
Ingelvac PRRS® MLV
Challenge Control (non-vaccinated)
Ingelvac PRRS® MLV (no challenge)
Days
% P
CR
Pos
itive
Figure 2. Percentage of viremic pigs per treatment group challenged with 2 logs
Results – Pyrexia/Fever· At each challenge dose Ingelvac PRRS® MLV vaccinates
- Had significant decrease in fever days compared to non-vaccinates- Maintained lower average temperature compared to non-vaccinates
· At PRRSV challenge of 2 logs or less- Post-challenge temperatures of Ingelvac PRRS ® MLV vaccinated pigs are
similar to temperatures of vaccinated non-challenged pigs
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
Challenge Control(non-vaccinated) 11.2 8.8 10.0 6.0 -
1 Statistically significant difference (P<0.05) in number of days pyrexic between groups based on model prediction
Results – Pyrexia/Fever
27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 4239.2
39.4
39.6
39.8
40.0
40.2
40.4
40.6
40.8
Ingelvac PRRS® MLV
Challenge Control (non-vaccinated)
Ingelvac PRRS® MLV (no chal-lenge)
Days
Deg
rees
(C°)
Figure 3. Average daily temperature per treatment group challenged with 4 logs of PRRSV
Results – Pyrexia/Fever
At PRRSV challenge of 2 logs or less• Post-challenge temperatures of Ingelvac PRRS ® MLV vaccinated pigs are similar
to temperatures of vaccinated non-challenged pigs• Consequences of challenge in vaccinates similar to non-challenged pigs
27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 4239.039.239.439.639.840.040.240.440.640.841.0
Ingelvac PRRS® MLVChallenge Con-trol (non-vac-cinated)Ingelvac PRRS® MLV (no chal-lenge)
Days
Deg
rees
(C°)
Figure 4. Average daily temperature per treatment group challenged with 2 logs of PRRSV
Results – Pyrexia/Fever
• Significant decrease in days pyrexic - vaccinates compared to non-vaccinates at each challenge dose
• Days pyrexic decreased as challenge dose decreased in both vaccinated and non-vaccinated groups
Figure 5. Number of Days Pyrexic by Group and Challenge Dose
Results – Average Daily Weight Gain · Ingelvac PRRS® MLV vaccinated groups had higher ADWG
compared to non-vaccinated challenge controls @ all challenge doses- Statistically significant (P<0.05) in the 3, 2, and 1 log challenge groups &
at P<0.07 in the 4 log challenge group· Measurable and negative ADWG impact in non-vaccinated
challenged groups at all challenge doses - No significant difference in ADWG across all challenge doses in non-
vaccinated groups
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
Challenge Control(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
Results – Average Daily Weight Gain · ADWG of Ingelvac PRRS® MLV vaccinated groups
challenged w/ 2 logs of PRRSV or less was numerically similar to the ADWG of vaccinated non-challenged group- Limited post-challenge ADWG impact in vaccinated pigs- Consequences of challenge in vaccinates similar to non-
challenged pigs
1 Statistically significant difference (P<0.05) in ADWG between Ingelvac PRRS® MLV and Challenge control groups based on model prediction
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
Challenge Control(non-vaccinated) 1.18 1.06 1.15 1.23 -
Results – Average Daily Weight Gain
· Significant increase in ADWG in vaccinates based on challenge dose- 0.085 increase in ADWG for
each one log decrease in challenge dose
· Measurable and negative ADWG impact in non-vaccinated challenged groups at all challenge doses - No significant difference in
ADWG across all challenge doses in non-vaccinated groups
Figure 6. Average Daily Weight Gain - Days 28-70 by Group and Challenge Dose
Summary – Take Home Message
• Objective of study was to evaluate effect of PRRSV challenge dose in vaccinated pigs
• In this heterologous PRRSV challenge study Ingelvac® PRRS MLV vaccinated pigs demonstrated:- Reduction in viremia compared to challenge controls at all
challenge doses- Reduction in fever compared to challenge controls at all challenge
doses- Increased ADWG compared to challenge controls at all challenge
doses- Mitigation of the negative consequences of PRRSV infection
compared to non-vaccinated challenged pigs at all challenge doses
Summary – Take Home Message
· For all endpoints – there was little indication of a difference between 0 (no challenge), 1 and 2 log challenge in vaccinated pigs- Indicating a challenge dose effect in vaccinated pigs- At a challenge of 2 logs or less, the consequences of
challenge in vaccinated pigs were similar to non-challenged pigs
· Conversely, in non-vaccinated pigs, the post-challenge viremia and impact on ADWG were similar across all challenge doses- Indicating no challenge dose effect in non-vaccinated pigs- Measureable & negative impact at all challenge doses in
non-vaccinated pigs
Summary – Take Home Message
· As in previous studies; this study is another example demonstrating the ability of Ingelvac PRRS® MLV vaccine to protect against a relevant PRRSV challenge and mitigate the biologic consequences of infection
· Based on challenge dose, the consequences of challenge in vaccinated pigs can be similar to non-challenged pigs
· Relevance in the field- Implementation of “system-based” and “area/region
based” control programs- Limiting the consequences of infection