Evaluation of porcine reproductive and respiratory syndrome virus (PRRSV) challenge dose in vaccinated pigs

The study demonstrates a challenge dose effect in vaccinated pigs; as challenge dose decreases, the mitigation of the consequences of infection improves.

01-03-2016


Article by:
G. Haiwick; A. Neubauer, J. Hermann, M. Roof, PhD; B. Fergen, R. Philips

Introduction
The swine industry continues to experience health challenges and economic losses due to PRRSV infections of sow farms and growing pigs.1 The infectious dose of PRRSV by intranasal, intramuscular and aerosol routes has been shown to be very low, confirming PRRSV to be highly infectious.2,3,4 Ingelvac PRRS® MLV has demonstrated protection against heterologous PRRSV challenge and can significantly reduce PRRSV induced lung lesions and mitigate the consequences of infection following challenge.5 The objective of this study was to evaluate the effect of PRRSV challenge dose in Ingelvac PRRS® MLV (BIVI-Boehringer Ingelheim Vetmedica, Inc., St. Joseph, MO) vaccinated pigs in a respiratory challenge model.  
 
Materials and methods
Experimental Design: A randomized, blinded vaccination-challenge study was performed in ninety, three week old pigs from a PRRS naïve source, and confirmed PCR negative for PRRS. The study consisted of five treatment groups of pigs. Groups 1-5; n = 10 per group, were vaccinated with Ingelvac PRRS® MLV (2 ml I.M. per label recommendations). Groups 1-5 were vaccinated on day 0.  Forty pigs served as non-vaccinated challenge controls (Groups 1-4; n = 10 per group) and were housed separately from any vaccinates during the vaccination phase. The study design is summarized in Table 1.
 
Challenge: Groups 1-4 were challenged on day 28 intranasally with 2.0 ml (1.0 ml/nostril) of inoculum of virulent PRRSV SDSU-73. Housing during the challenge phase was by group and PRRSV challenge. Group 5 was an Ingelvac PRRS® MLV vaccinated and non-challenged treatment group.
 
Viremia: Blood was collected from all pigs on days 0, 7, 14, 21, 28, 31, 33, 35, 38, 42, and weekly thereafter until day 70 to assess the serologic response and viremia. Viremia testing for PRRSV was assessed by BIVI-Health Management Center (HMC Ames, Iowa) using Quantitative PCR and results were reported as “positive” or “negative”.
 
Temperature: Rectal temperatures were collected on the day prior to challenge (day 27), and daily for 14 days until day 42. Pyrexia was defined as a rectal temperature > 40.0° C.
 
Weight Gain: Pigs were weighed at day 0, day of challenge (day 28), and termination of the study (day 70) to assess daily weight gain (ADWG).


 
Statistics: Results were summarized via descriptive statistics by day, challenge dose and group. For number of days pyrexic and ADWG post-challenge, a linear regression model incorporating treatment and challenge dose was utilized, with model simplification based on stepwise removal of non-significant model terms. A P-value < 0.05 was used to indicate statistical significance.
 
 
Results

Viremia:  Following challenge, all pigs in the Ingelvac PRRS® MLV vaccinated treatment groups 1 and 2, (4 and 3 log challenge), became viremic by day 31. Following day 42 (14 days post-challenge) of the study, viremia begins decreasing in the vaccinated pigs until termination of the study on day 70. From day 42 to day 70 of the study, the vaccinated pigs in groups 1 and 2 demonstrate less percent PCR positive pigs than the non-vaccinated challenge control pigs in groups challenged with 4 and 3 logs of virus, indicating a reduction in post-challenge viremia in vaccinated pigs. As seen in groups 1 and 2, the Ingelvac PRRS® MLV vaccinated pigs in groups 3 and 4, (2 and 1 log challenge), demonstrate less percent PCR positive pigs than the non-vaccinated challenge control pigs. The pattern of viremia following challenge in vaccinated groups 3 and 4 was similar to the vaccinated non-challenged pigs in group 5. As the challenge dose decreases the percentage of viremic pigs in the vaccinated pigs in the vaccinated groups decreases. At all challenge doses, the non-vaccinated and challenged pigs show a similar post-challenge viremia profile.
Post-challenge viremia results are summarized in Figures 1 and 2.

 
Temperature: At each challenge dose, there was a statistically significant decrease in the number of days pyrexic post-challenge between vaccinated and non-vaccinated treatment groups. The Ingelvac PRRS® MLV vaccinated pigs maintained a lower average temperature throughout the challenge phase of the study; (days 28-42), when compared to the non-vaccinated challenge controls at all challenge doses. At PRRSV challenge doses of 2 logs or less, the post-challenge average temperatures of the Ingelvac PRRS® MLV vaccinated pigs are similar to the temperatures of the vaccinated non-challenged pigs.   
Post-challenge temperature results are summarized in Table 2 and Figures 3, 4 and 5.  
 
Average daily weight gain: ADWG was evaluated for the post-challenge portion of the study (days 28-70) for all treatment groups. The Ingelvac PRRS® MLV vaccinated groups demonstrated higher ADWG compared to the non-vaccinated challenged control groups at all challenge doses. The difference in ADWG between vaccinates and non-vaccinates was statistically significant in the 3 log, 2 log and 1 log challenge dose groups. The ADWG for the Ingelvac PRRS® MLV vaccinated groups challenged with 4 logs, 3 logs, 2 logs and 1 log of PRRSV were 1.41, 1.29, 1.70 and 1.64 lbs/day respectively; compared to ADWG of the non-vaccinated challenged control groups challenged with 4 logs, 3 logs, 2 logs and 1 log of PRRSV at 1.18, 1.06, 1.15 and 1.23 lbs/day respectively. There was a significant increase (P < 0.05) in the ADWG based on the challenge dose in the Ingelvac PRRS® MLV vaccinated groups, as the ADWG increased 0.085 for each one log decrease in challenge dose. There was a measurable negative ADWG impact in the non-vaccinated challenged groups at all challenge doses, with no significant difference in ADWG across all challenge doses. The vaccinated non-challenged group demonstrated an ADWG of 1.67 lbs/day, indicating the virulent PRRSV challenge has a biologic impact as measured by ADWG when compared to non-vaccinated challenge groups. The ADWG of the Ingelvac PRRS® MLV vaccinated groups challenged with 2 logs of PRRSV or less was numerically similar to the ADWG of the vaccinated  non-challenged group, indicating limited post-challenge ADWG impact in vaccinated pigs. 
The ADWG results are summarized in Table 3 and Figure 6. 
 
Discussion and conclusions
The objective of this study was to evaluate the effect of PRRSV challenge dose in vaccinated pigs. The PRRSV challenge isolate used in this study was SDSU-73, and is 89.7% homologous to Ingelvac PRRS® MLV based on ORF 5 sequence. In this study, Ingelvac PRRS® MLV vaccinated pigs demonstrated mitigation of the consequences of PRRSV infection compared to non-vaccinated challenge pigs at all challenge doses with a reduction in post-challenge viremia, temperature and increased ADWG. The Inglevac PRRS® MLV vaccinated groups had better ADWG compared to non-vaccinated challenge controls at all challenge doses demonstrating that vaccination mitigated the negative impact of the PRRSV challenge on ADWG. Compared to non-vaccinated challenged pigs, the increase in ADWG of the Ingelvac PRRS® MLV vaccinated pigs was statisticially significant (P<0.05) in the 3, 2 and 1 log challenge groups, and at P<0.07 in the 4 log challenge group. The number of days pyrexic in the non-vaccinated challenge control group seemed to be affected by challenge dose, whereas ADWG seemed not to be affected.  For all endpoints, there was little indication of a difference between 0, 1 and 2 log challenge in vaccinated animals, indicating that there is a challenge dose effect in vaccinated pigs, and at a challenge of 2 logs or less, the consequences of challenge in vaccinated pigs were similar to non-challenged pigs. Identification of the PRRSV strain measured by post-challenge viremia is in process at the time of the writing of this paper. Conversely, in the non-vaccinated challenged pigs, the post-challenge viremia and impact on ADWG were similar across all challenge doses, indicating no challenge dose effect and a measurable impact at all challenge doses in non-vaccinated pigs.  






This study is another example demonstrating the ability of Inglevac PRRS® MLV vaccine to protect against a relevant PRRSV challenge and mitigate the biologic consequences of infection. The study also demonstrates a challenge dose effect in vaccinated pigs; as challenge dose decreases, the mitigation of the consequences of infection improves. Based on challenge dose, the consequences of challenge in vaccinated pigs can be similar to non-challenged pigs. The results of this study have relevance in the field as implementation of vaccine in a systematic and coordinated methodology along with the other complimentary components for PRRS control in system-based and area-regional control programs can mitigate the consequences of PRRSV infection subsequently improving health and performance.
 
 
                        
 
References
1.       Holtkamp, D., et al. 2013. Assessment of the economic impact of porcine reproductive and respiratory syndrome virus on United States pork producers. J Swine Health and Prod. 21(2):72-84.
2.       Yoon, K. J., et al. 1999. Effect of challenge dose and route on porcine reproductive and respiratory syndrome virus (PRRSV) infection in young swine. Vet Res. 30:629-638.
3.       Hermann, J., et al. 2007. Susceptibility of young pigs to porcine reproductive and respiratory syndrome virus (PRRSV) infection by aerosol route of exposure. AASV Proceedings.
4.       Cutler, T., et al. 2010. Median infection dose (ID50) of PRRSV isolate MN-184 for young pigs via aerosol exposure. IPVS Proceedings.
5.       Patterson, A., et al. 2013. Modified live PRRSV vaccination is efficacious following challenge with eight genetically diverse PRRSV isolates. A.D. Leman Swine Conference Proceedings.

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2016