Vaccination and Control of PRRS

Vaccination and Control of PRRS

Key Contributors Univ of Minnesota RP Mulupuri Zhengguo Xiao Craig Johnson Juan Li Sally Robinson Scott Dee Pipestone Vet Clinic Jeff Zimmerman Iowa State Paul Yeske Swine Vet Center Eric Nelson South Dakota State Mike Roof Boehringer Ingelheim Eric Vaughn Sponsors USDA CAP USDA NRI National Pork Board Minnesota Pork Board Boehringer Ingelheim Vetmedica University of Minnesota NIH NIDA Schulze Diabetes Institute Competing interests Patents

There are Two General Types of PRRSV Type 1 (European) Type 2 (North American) ORF5 Dendrogram The virulent viruses of Asia

There are Two General Types of PRRSV Feature Peak viral load Virulence respiratory Virulence reproductive Innate interferon induction Growth in MARC 145 Global distribution (wt virus) Global distribution (Live vaccines) Evolution rate Type 1 PRRSV Medium Low Medium No Very poor Europe, Korea, US Europe, Korea High Type 2 PRRSV High High High Yes Medium Asia, N and S America All continents High Type 2 PRRSV is the Key Problem in Asia

How Does PRRSV Move? Pigs Semen Transport People Needles Air

Routes of PRRS Infection PRRSV? PRRSV? Gilts PRRSV? Boar Stud Infected Animal Grow-Finish Semen Sow Herd Infected Pig Market PRRSV? Infected Piglet in Utero or After Birth Nurseries PRRSV? Standard USA production system. Multi-site, All in-all out, Unidirectional flow PRRSV goes where pigs go.

Disease Goes Where Pigs Go Interstate pig movements in the U.S.A. in 2001 Disease goes where pigs go.

Methods and Tools for PRRSV Control Negative Animals Negative Semen Biosecurity Clean Transport Herd Closure Air Filtration Health Management Vaccination

Clean and Disinfect Transport Vehicles Paul Yeske Swine Vet Center

Biosecurity Down Time UMN and Purdue work showing just have to change clothes and boots and wash hands to avoid spread Paul Yeske Swine Vet Center

Preventing Disease: People Remove shoes in the initial entryway while sitting on the bench Without touching socks to the floor, swing feet over the bench to the other side Paul Yeske Swine Vet Center

Getting Rid of PRRSV Herd Closure: Mass vaccinate or inoculate entire herd to PRRSV and close to animal entry for >250 days. 15 multiplication herds were preloaded with gilts and closed for an average of 260 days. After closure, all farms tested negative for PRRSV by PCR and have remained negative for 4 years. Torremorrell, Moore, Christianson. 2002. Establishment of a herd negative for porcine reproductive and respiratory syndrome virus (PRRSV) from PRRSV-positive sources. J Swine Health Prod. 10:153-160. Schaefer and Morrison. 2007. Effect on total pigs weaned of herd closure for elimination of PRRSV. J Swine Health Prod. 15:152 155. Herd Closure Gets Rid of PRRS

Biosecurity with Air Filtration Field experience includes 21 boar studs, 8 sow farms, 1 finisher, 1 research farm (Swine Vet Clinic). Air filtration prevented PRRS transmission during demonstrated episodes of local area spread. Also, no mycoplasma breaks, and 2 SIV breaks in 3 years field experience. Spronk G, Otake S, Dee S. 2010. Prevention of PRRSV infection in large breeding herds using air filtration. Vet Rec. 166:758-9. Photo: Paul Yeske Air Filtration Keeps PRRS Out

Why Do we Care So Much? PRRS outbreaks are really expensive!

Pathogenesis News: Recent Isolates are Really Virulent Reproductive PRRS Acute Outbreak Nov 2007, 2,000 naïve sow herd Sow death loss >60% Pre-weaning mortality 100% Direct losses ~$750,000 or >5 million RMB

The Role of Vaccination in Control of PRRS PRRSV? Gilts Sow Herd Vaccine Protects against Severe Clinical Signs at All Stages of Production PRRSV? Grow-Finish Market PRRSV? Nurseries PRRSV? Standard USA production system. Multi-site, All in-all out, Unidirectional flow PRRSV goes where pigs go.

The Role of Vaccination in Control of PRRS Gilts Sow Herd Protects Naïve Pigs going into a Positive Herd or a Pig-Dense Region PRRSV? Grow-Finish Market PRRSV? Nurseries PRRSV? Standard USA production system. Multi-site, All in-all out, Unidirectional flow PRRSV goes where pigs go.

The Role of Vaccination in Control of PRRS Gilts PRRSV? Sow Herd Reduces Disease Losses in an Outbreak Grow-Finish Market PRRSV? Nurseries PRRSV? Standard USA production system. Multi-site, All in-all out, Unidirectional flow PRRSV goes where pigs go.

Attenuated Live PRRSV Cross-Protects Against Heterologous Challenge Opriessnig et al. 2005. J. Swine Hlth. Prod. 13:246-253. Gross and microscopic lung lesions induced by PRRSV in vaccinated and unvaccinated groups at 14 days post PRRSV inoculation. Group % Gross lesions Microscopic lesions (mean±standard 0-6 scale error) (mean±standard err or ) 1 - Vaccinated + SDSU73 4.2±0.8 A,B 1.8±0.2 A 2 - Vaccinated + VR2385 8.4±2.5 A,D 1.6±0.2 A 3 - Vaccinated + Mn-01-A1 3.6±1.4 A,B 2.2±0.2 A 4 - Unvaccinated + SDSU73 41.6±7.5 C 5.1±0.2 B 5 - Unvaccinated + VR2385 18.4±3.5 D 4.1±0.2 C 6 - Unvaccinated + Mn-01-A1 49.2±4.9 C 4.8±0.3 B,C 7 - Unvaccinated/Unchallenged 0.1±0.1 B 0.0±0.2 D 8 - Vaccinated control 0.3±0.3 A,B 1.3±0.3 A,D Different superscripts within each column indicate significantly different values (p<0.001).

Cross-Protection is Reproducible Ingelvac PRRS MLV ATP Challenge Isolate Difference Vac Non-Vac Reduction VR2332 0% 10 38-28 NADC 6% 1 32-31 17198-6 1-4-2 10% 1 15-14 17198-6 1-4-2 10% 1 26-25 SDSU73 11% 0 38-37 SDSU73 11% 16 53-37 SDSU73 11% 8 47-39 FI 3 1-5-2 12% 1 18-17 MN 1-8-4 13% 5 33-28 MN 1-8-4 13% 2 18-15 MN 1-8-4 13% 30 36-6 MN 1-8-4 13% 10 36-26 MN 1-8-4 13% 12 30-18 FI 2 1-4-4 14% 37 53-16 SDSU73 10% 18 70-52 SDSU73 10% 37 82-45 SDSU73 10% 27 47-19 VR2332 10% 6 23-18 FI 1-18-2 13% 14 58-44 FI 3 1-5-2 13% 1 18-17 MN 1-8-4 14% 9 63-54 Amy Patterson and Jose Angulo Boehringer Ingelhiem Vetmedica

1. All Experiments Show Protection (Reduction in Lesions) 2. Average Effect is the Same Regardless of Genetic Difference 0 Scatterplot of Lung L Red vs Het -10 Lung Lesion Reduction Lung L Red -20-30 -40-50 -60 0,00 0,02 0,04 0,06 0,08 0,10 0,12 Het Percent Genetic Difference versus Challenge Virus 0,14 Amy Patterson and Jose Angulo Boehringer Ingelhiem Vetmedica

Immune Intervention as Treatment in a Nursery Philips et al. 2007 International PRRS Symposium

Preventive/Therapeutic Vaccination: Nursery PRRS Positive Vaccinated Nurseries Before Vaccination Total # Out % Mortality After Vaccination 2005 Closeout Data: Immune Intervention Equals PRRS-Negative Production PRRS Negative Non-vaccinated Nurseries In Wt. Out Wt. ADG FE 331,462 2.65% 13.73 54.94 0.89 1.56 337,810 3.04% 13.61 54.01 0.88 1.62 Waddell, J. 2008. Pig vaccination as an essential part of a comprehensive PRRS control program. AASV meeting. San Diego, USA. Conclusion: Live Virus Vaccination Controls PRRS

Vaccines against PRRSV Name Description Introduction Manufacturer Comments Efficacy Citations * Ingelvac MLV Cell-culture attenuated 1994 Boehringer Ingelheim Also known as ResPRRS, 2 4 form of strain VR-233 2 Vetmedica ResPRRS Rep r o Ingelvac PRRS KV Inactivated form of strain Boeringer Ingelheim PRIMEPAC PRR S VR-2332 Cell-culture attenuated form of a Nebraska field strain Vetmedica 1996 Schering Ploug h Discontinued in 2000 due to patent infringemen t Ingelvac ATP Cell-culture attenuated form of strain JJ1884 2004 Boehringer Ingelheim Vetmedica 2 Suvaxyn PRRS? Fort Dodge Animal Health Discontinued? AmervacPRRS? Laboratories Hipr a 1 Porcilis PRRS? Intervet 8 Pyrsvac-183 SYVA Laboratorie s 1 Inactivated cell culture Bayer lysate Progressis Inactivated vaccine Meria l Only in Europ e 13??? PRRomiSe Inactivated vaccine Intervet? 0 Autogenous Inactivated field isolate s Newport Laboratories 20% of market in 2000, low 3 vaccines and other s today MJPRR S MJ Biologics In combination with a live vaccine or virus inoculatio n 0 PRRSV RS AAV-GP5/6 vectored vaccine 2009 Sirrah Bios 0 BSL-PS 100 MLV No information availab l e Bestar Laboratories Pte Ltd. Singapore BSL-PS 100 Killed vaccin e No information availab l e Bestar Laboratories Pte Ltd. Singapore SuiShot PRRS Killed vaccin e s No information availab l e ChoongAng Vaccine Laboratories Co. Ltd South Korea Suivac PRRS-I N Killed vaccin e VD-E1, VD-E2, VD-A1 Dyntec spol. S.r. o. Czech Republ i c Suivac PRRS-I n e Killed vaccin e VD-E1, VD-E2 Dyntec spol. S.r. o. Czech Republ i c Suipravac Killed vaccin e 5710 ( adapted ) Hipra Spain/Singapore Amervac PRRS MLV VP046 BIS Hipra Spain/Singapore?? MLV No information availab l e Kaketsuken Japan PRRS vaccine Killed vaccin e NVDC-JXA1 PRRS Vaccine, Live (R98 Strain) Lan Yi Ling Qilu Animal Health Products Factory China MLV R98 strai n? China 1

Vaccines against PRRSV Name Description Introduction Manufacturer Comments Efficacy Citations * Ingelvac MLV Cell-culture attenuated 1994 Boehringer Ingelheim Also known as ResPRRS, 2 4 form of strain VR-233 2 Vetmedica ResPRRS Rep r o Ingelvac PRRS KV Inactivated form of strain Boeringer Ingelheim PRIMEPAC PRR S VR-2332 Cell-culture attenuated form of a Nebraska field strain Vetmedica 1996 Schering Ploug h Discontinued in 2000 due to patent infringemen t Ingelvac ATP Cell-culture attenuated form of strain JJ1884 2004 Boehringer Ingelheim Vetmedica 2 Suvaxyn MANY PRRS? OF Fort Dodge THESE Animal Discontinued? Health AmervacPRRS? Laboratories Hipr a 1 Porcilis PRRS? Intervet 8 Pyrsvac-183 SYVA Laboratorie s 1 Inactivated cell culture Bayer lysate Progressis Inactivated vaccine Meria l Only in Europ e 13??? VACCINES PRRomiSe Inactivated vaccine ARE Intervet? NO 0 Autogenous Inactivated field isolate s Newport Laboratories 20% of market in 2000, low 3 vaccines and other s today MJPRR S MJ Biologics In combination with a live 0 vaccine or virus inoculatio n PRRSV RS AAV-GP5/6 vectored 2009 Sirrah Bios 0 vaccine Bestar Laboratories Pte BSL-PS 100 MLV No information availab l e Singapore Ltd. GOOD Bestar Laboratories Pte BSL-PS 100 Killed vaccin e No information availab l e Singapore Ltd. ChoongAng Vaccine SuiShot PRRS Killed vaccin e s No information availab l e South Korea Laboratories Co. Ltd Suivac PRRS-I N Killed vaccin e VD-E1, VD-E2, VD-A1 Dyntec spol. S.r. o. Czech Republ i c Suivac PRRS-I n e Killed vaccin e VD-E1, VD-E2 Dyntec spol. S.r. o. Czech Republ i c Suipravac Killed vaccin e 5710 ( adapted ) Hipra Spain/Singapore Amervac PRRS MLV VP046 BIS Hipra Spain/Singapore?? MLV No information availab l e Kaketsuken Japan PRRS vaccine Killed vaccin e NVDC-JXA1 Qilu Animal Health Products Factory China PRRS Vaccine, Live (R98 Strain) Lan Yi Ling MLV R98 strai n? China 1

Qualities of a Good PRRS Vaccine Attenuated (modified) live virus (MLV) Killed and subunit products do not protect Attenuated (modified) should be safe Field isolates are virulent Good technical support Timing and use of PRRS vaccines takes skill

Scortti et al. 2007. Failure of an inactivated vaccine against porcine reproductive and respiratory syndrome to protect gilts against a heterologous challenge with PRRSV. Vet Record 161, 809-813. Killed Vaccines do not Protect Against PRRSV

Killed Vaccine Does Not Reduce PRRS Infection +/ VR2385 PRRSV KV 0 14 28 42/63 Days of Treatment Examine I No Treatment II KV PRRomiSe d 14+28 III VR2385 d 0 IV VR2385 d 0, KV d 14+28 V VR2385 d 0, KV d 7+21 Conclusion: Live, replicating virus is required for protective immunity.

Protection from PRRS: GP5 Vaccine Enhanced Disease Prieto et al. 2010. Immunisation of pigs with a major envelope protein sub-unit vaccine against porcine reproductive and respiratory syndrome virus (PRRSV) results in enhanced clinical disease following experimental challenge. Vet J. [Epub ahead of print] Subunit Vaccine Did Not Protect; It Made Disease Worse

Protection from PRRS: Subunit and Vectored Vaccines give Little Protection or Increase Disease 90 90 80 80 Percent of Sows/Piglets 70 60 50 40 30 20 70 60 50 40 30 20 Total Number of Days No challenge control No vaccine control Subunit (MJ) Vectored (Sirrah) Modified live (ATP) 10 10 0 Sows PCR+ at 8 days Sows Days off feed Piglets Failure to wean 0 Darwin Reicks, 2010 Leman Conference Conclusion: Live, replicating virus is required for immunity

Limitations of a Good PRRS Vaccine IT ONLY WORKS AGAINST PRRS DIAGNOSTICS ARE IMPORTANT IT DOES NOT REPLACE SANITATION, GENETICS, OR GOOD ANIMAL CARE

A Few Words about Diagnostics Health +/ Viremia +/ Real time RT-PCR IDEXX ELISA S/P ratio Reproduction +/ PSY, PWSY Growth +/ ADG, FE Financial +/ Not Quantitative $, RMB Quantitative Quantitative Observations Give More Information

Advanced Swine Production Practices Multi-site, All-in All-out production with unidirectional flow Artificial insemination with semen from high-health, PRRSV-negative boar stud PRRSV-free replacement gilts. High quality complete biosecurity program. Goal: PRRSV-free production Reasons: Profitability, humane care, responsible management

Final Comment What We Can Do to Control PRRS: Use All of the Tools Multi-site, All in-all out, production. High biosecurity and sanitation. Good veterinary practice. Good animal management. Good diagnostics. Effective use of live, safe, attenuated vaccines. Good recordkeeping and financial data.