Han Smits, DVM, MAgSc

Technical Director Swine EMEA & CoE

Your logo

Thursday 4th June 2015

Prime-boost concept for an

improved PRRSv control

Thursday 4th June 2015

Program

PRRS virus

Genetics of PRRSv

Immunity against virusses

/ PRRSv

New concept for PRRSv control Pink Pig Page

PRRS virus

In Europe since 1991

Reproduction and respiratory problems

Genotype 1 (European) and genotype 2 (American)

Costs

USA: PRRS (2012) 600 x 106 € (AASV, 2013)

EUROPE: Netherlands / Spain: €60,- till €350,-

No complete control possible: management and

vaccination (MLV and KV)

PRRS: 4-5 subtypes in Europe

In an ideal world: immune defense against viruses

Viral infection : protective

immune response

TH17

TH2

TH1

Treg

Naïve CD4+ cells

Cytotoxicity IFNg & TNFa

Infected cell lysis Virus destruction

B cell Neutralising Ab

Virus blockage

Dendritic+ cells

PRRS virus modulates the immune system

Viral infection : protective

immune response

TH17

TH2

TH1

Treg

Naïve CD4+ cells

Cytotoxicity IFNg & TNFa

Infected cell lysis Virus destruction

B cell Neutralising Ab

Virus blocage

Mature macrophages and Dendritic

cells

X X

X

PRRSV survives and replicates

concomitant infections

Treg X

PRRSV

CD4+ T cells

X Th1 X

Build up immunity against

PRRSv??

A new concept

Studies on repeated

vaccination … ALL IN US (USING AMERICAN-TYPE STRAINS)

Days

GROUPS 0 7 14 28 42 44 54

Non-vaccinated X

Necro

psy

INV INV INV X

MLV MLV X

MLK MLV INV INV X

KML INV INV MLV X

EXPERIMENTAL

CONDITIONS • Highest production of

Neutralizing Antibodies

• qRT-PCR negative sera

• Less lesions in lungs

(Nilubol et al., 2007) IN FARMS (SOWS) • MLV + MLV

• MLV + INV +INV

• INV + INV + INV

Highest production of NA

(Thacker et al., 2004)

Most remarkable results

Comparison different vaccination

schedules against PRRSv

EXPERIMENT 1

AIM: Effect of repeated vaccinations using inactivated vaccine

EXPERIMENT 2

AIM: Development of PRRSv-specific immune responses after attenuated

vaccine (MLV) primo-immunization followed with a MLV or INV recall

vaccination.

Díaz et al. 2013. The Veterinary Journal.

CReSA experiment 1.

conclusions

1. Significant increase of cell-mediated immunity and

neutralizing antibodies (NA) production

2. Development of memory cells

3. After the challenge, significant increase in the NA

Evaluation of the humoral responses

Virological analysis after challenge

Evaluation of the cell-mediated immune response

Experiment 2: MLV followed by

a MLV or INV VACCINATION SCHEDULE BALANCE SAFETY/EFICACY

(n=32) Months of age

GROUP 1,5 4,5 5,5 6,5 7,5

A MLV MLV - CH END

B MLV INV - CH END

C MLV INV INV CH END

D - - - CH END

MLV = Attenuated

PRRSv + Adjuvant

INV = Inactivated

PRRSv + Adjuvant

Ch= Challenge.

Strain2749, EU

type. ORF5 99%

similar to LV

Conclusions

After a MLV primo-vaccination: INV re-vaccination induced a significant increase in the

development of cell-mediated immunity (memory

response).

The increase was significantly higher than MLV re-

vaccinated pigs.

After the challenge, MLV+INV+INV group developed

the highest PRRSv-specific immune responses (cell-

mediated immunity and neutralizing antibodies).

VACCINATION SCHEDULE MLV+INV BALANCE SAFETY/EFICACY

An exciting innovation in

vaccination

14

What is it? A strategy to enhance immune responses especially cell-

based immunity

Immunize using successively 2 “different but related”

vaccines

15

Prime Boost

same

different

The classical

strategy

The innovation

How does it work?

Focus immune responses on protective antigens (●) while

limiting responses against other antigens (●, ●)

16

Build up immunity against PRRSv??

A new vaccination strategy

MERIAL approach

In our market MLV PRRS is the most often used vaccine

Still too many farms with problems

Merial’s new approach for these farms:

MLV and INV; use MLV as “conditioned field virus circulation”

Higher immunity due to memory cells: boostering

High MDA in combination with management improvements

(multi site, age segregation, batch management…) makes it

possible to produce PRRS negative off-spring from a PRRS

positive sow herd and reduce PRRS impact

Research on the prime + boost

concept

What is the fundamental effect on the prime + boost

concept in immunology / immunity, viremia and virus

circulation?

What is the effect on virus controle and disease controle?

What is the effect on reproduction in sows and

production in the piglets?

Alternative setups?

Dekens et al., ESPHM 2012

300 sows F-to-F farm

D6 MLV vaccination

Vaccination with an INV vaccine at

day 90 of pregnancy

Results:

Induced higher MDA

Delayed circulation of PRRS in piglets

until 8 woa

No seroconversion untill 10 woa

Results

Results

Defoort et al., IPVS 2014

1.200 sows F-to-F farm

3 times / yr MLV

D60 MLV + D90 INV

Results:

Soon after start of INV serological

and clinical stabilization in piglets

Antibiotic reduction

In a later phase also the PRRS

circulation stabilized in the sow herd

Stabilization of PRRSV circulation in a farm using a vaccination program with PROGRESSIS®

at the end of gestation

P. Defoort1, T. Meyns

2, S. Van Poucke

2, V. Dekens

2, F. Joisel

3

1Provet DAP, Torhout, Belgium;

2MERIAL NV, Diegem, Belgium;

3MERIAL S.A.S., Lyon, France;

pascal.defoort@provet.be

Introduction

PRRS is considered as the most important economic

viral disease of intensive swine production. It is

characterized by reproductive failure in sows and

respiratory disease and poor production in nursery

piglets. PROGRESSIS®

, an inactivated EU type PRRSV

vaccine, was shown to reduce the number of v iraemic

piglets, born from vaccinated sows (1). Additionally, it

has been shown that maternal immunity can protect

piglets during their nursery period by vaccination of

sows at day 60 (2) o r at day 90 of pregnancy with

PROGRESSIS (3). The present case report describes the

stabilization of a conventional swine farm infected with

PRRSV by vaccinating the sows and gilts during almost

2 years at day 60 with an EU type MLV vaccine and at

day 90 of gestation with PROGRESSIS.

Materials and Methods

This case involved a 1200-sow farrow-to-finish farm,

with 5 production lines of a recent date. Genetics are

Danbred sows x Piétrain. At the time of the problems,

the sows and gilts were vaccinated in block with a EU

type MLV PRRSV vaccine 3 times a year. The nursery

piglets were housed in 2 large buildings.

Results

In January 2012, severe problems associated with

PRRSV were d iagnosed. The problems included early

births, weak and death born piglets and problems in the

nursery room, bad production results (piglet mortality

around 4.5%) and increased use of antibiotics. At that

time, serological data (IDEXX ELISA) confirmed

circulat ion of PRRSV in sows and gilts (Table 1) and in

piglets (Table 2). PRRSV was also detected in blood by

PCR in piglets of 3 and 7 weeks of age.

Table 1. PRRSV S/P ratios in sera collected from sows

and gilts between Jan 2012 and Oct 2013 01/2012 11/2012 10/2013

Gilts 1.78 3.18 1.63

2.26 1.52 1.44

2.15 1.12 0.96

0.87 2.14 1.69

2.51 3.84 1.92

Sows 0.9 4.23 2.29

0.53 1.58 2.22

1.6 1.87 2.02

3.16 3.25 2.14

1.26 2.49 2.4

To solve these problems, the vaccination program in the

sows was adapted to vaccination with an EU type MLV

vaccine at day 60 combined with PROGRESSIS at day

90 of gestation.

In November 2012, around 11 months after the start of

the adapted vaccination program, a clinical and

serological stabilizat ion of PRRSV circulation in the

nursery piglets was observed (Table 2). At that time, the

serological pro file in sows and gilts was still indicative

for recent circulat ion of PRRSV (titers > 3). In October

2013, after 22 months of vaccinating all sows and gilts

repeatedly at day 90 of gestation with PROGRESSIS,

also the titers of the sows and the gilts became uniform

(Table 1), while S/P rat ios in pig lets at the end of

nursery remained low. At the end of 2013, the mortality

in the nursery was reduced to ≈ 2%.

Table 2. PRRSV S/P ratios in sera collected from

piglets of 6 and 10 weeks of age between Jan 2012 and

Oct 2013 01/2012 11/2012 10/2013

Piglets of 6 weeks of age

2.14 2.96 1.04

1.11 1.54 1.60

2.35 1.15 1.88

2.34 0.69 2.57

2.19 2.8 2.30

Piglets of 10

weeks of age

2.55 0.28 0.67

2.46 0.78 0.17

3.06 0.08 0.08

2.25 0.34 0.55

2.87 0.58 0.56

Discussion and conclusion

After the start of the vaccination with PROGRESSIS at

day 90 of pregnancy, there was a relative quick recovery

of the production results in the nursery due to a lower

infection pressure. After 22 months, there was in

addition a remarkable stabilizat ion of the PRRSV

circulat ion in the sows and gilts. These results indicate

that the use of PROGRESSIS just before farrowing can

be an efficient tool to induce an increased maternally

derived immunity in piglets and to control virus

circulation at herd level in order to stabilize a herd.

References

1. Joisel F. et al. 2001. Pig Journal 48, 120-137

2. Geldhof M.F. et al. 2013. Vet Microbiol 167, 260-271

3. Dekens V. et al. 2013. ESPHM, Edinburg, UK, P178

®PROGRESSIS is a registered trademark of Merial in

Belgium.

Results

Willems et al., ESPHM Nantes 2015

400 sows F-to-F unit, Brittany

D 6 MLV, still severe PRRS problems

+ D 90 INV

Results:

No PRRSv circulation till at least 14

woa

Clear reduction of PRRS associated

clinical signs

Thank you very much!

Questions?