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