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Evaluation of PRRSV challenge dose in
vaccinated pigs
AASV Annual Meeting
Technical 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 pigs
1. 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. Inglevac
PRRS® MLV
Vaccinated
Pigs
(2ml IM)
No. Non-
vaccinated
Challenge
Control
Pigs
PRRSV SDSU-
73
Challenge
Dosage
(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 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
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
0%
20%
40%
60%
80%
100%
120%
28 31 33 35 38 42 49 56 63 70
%PCRPositive
Days
Ingelvac PRRS® MLV
Challenge Control (non-
vaccinated)
Ingelvac PRRS® MLV
(no challenge)
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
0%
20%
40%
60%
80%
100%
120%
28 31 33 35 38 42 49 56 63 70
%PCRPositive
Days
Ingelvac PRRS® MLV
Challenge Control (non-
vaccinated)
Ingelvac PRRS® MLV
(no challenge)
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
39.2
39.4
39.6
39.8
40.0
40.2
40.4
40.6
40.8
27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42
Degrees(C°)
Days
Ingelvac PRRS®
MLV
Challenge Control
(non-vaccinated)
Ingelvac PRRS®
MLV (no challenge)
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
39.0
39.2
39.4
39.6
39.8
40.0
40.2
40.4
40.6
40.8
41.0
27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42
Degrees(C°)
Days
Ingelvac PRRS®
MLV
Challenge
Control (non-
vaccinated)
Ingelvac PRRS®
MLV (no
challenge)
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

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Dr. Reid Philips - Comparative Efficacy Evaluation of Two Modified-Live PRRS Vaccines

  • 1. Evaluation of PRRSV challenge dose in vaccinated pigs AASV Annual Meeting Technical Partners Session February 28th, 2016
  • 2. Objective of Study  Evaluate the effect of PRRSV challenge dose in Ingelvac PRRS® MLV vaccinated pigs in a respiratory challenge model
  • 3. Primary Objective: Question?  In vaccinated pigs 1. 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?
  • 4. 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
  • 5. Study Design Group No. Inglevac PRRS® MLV Vaccinated Pigs (2ml IM) No. Non- vaccinated Challenge Control Pigs PRRSV SDSU- 73 Challenge Dosage (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
  • 6. 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
  • 7. 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
  • 8. 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 0% 20% 40% 60% 80% 100% 120% 28 31 33 35 38 42 49 56 63 70 %PCRPositive Days Ingelvac PRRS® MLV Challenge Control (non- vaccinated) Ingelvac PRRS® MLV (no challenge) Figure 1: Percentage of viremic pigs per treatment group challenged with 4 logs
  • 9. 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 0% 20% 40% 60% 80% 100% 120% 28 31 33 35 38 42 49 56 63 70 %PCRPositive Days Ingelvac PRRS® MLV Challenge Control (non- vaccinated) Ingelvac PRRS® MLV (no challenge) Figure 2. Percentage of viremic pigs per treatment group challenged with 2 logs
  • 10. 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
  • 11. Results – Pyrexia/Fever 39.2 39.4 39.6 39.8 40.0 40.2 40.4 40.6 40.8 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 Degrees(C°) Days Ingelvac PRRS® MLV Challenge Control (non-vaccinated) Ingelvac PRRS® MLV (no challenge) Figure 3. Average daily temperature per treatment group challenged with 4 logs of PRRSV
  • 12. 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 39.0 39.2 39.4 39.6 39.8 40.0 40.2 40.4 40.6 40.8 41.0 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 Degrees(C°) Days Ingelvac PRRS® MLV Challenge Control (non- vaccinated) Ingelvac PRRS® MLV (no challenge) Figure 4. Average daily temperature per treatment group challenged with 2 logs of PRRSV
  • 13. 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
  • 14. 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
  • 15. 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 -
  • 16. 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
  • 17. 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
  • 18. 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
  • 19. 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

Editor's Notes

  1. As has been demonstrated previously, Ingelvac PRRS consistently reduces post-challenge viremia against a current and highly virulent wild-type PRRSV
  2. At both 2 logs and 1 log challenge see very interesting results supporting aid in prevention of post-challenge viremia/infection
  3. At 3 and 4 log challenge, seeing what we expect from vaccine ……. Mitigation of consequences of infection At 2 logs and less challenge seeing same trends when measure viremia, fever, and ADWG …….. Aid in prevention of infection; no impact post-challenge to viremia, fever, ADWG in vaccinated pigs.
  4. 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