PRRSV situation and PRRSV type 1 vaccination in ...

PRRSV situation and PRRSV type 1 vaccination in Europe Hans Nauwynck

Ghent University Belgium

Laboratory of Virology Faculty of Veterinary Medicine

PRRSV situation in Europe Hans Nauwynck



Porcine Reproductive & Respiratory Syndrome Virus PRRSV • Classification

Order Nidovirales Family Arteriviridae

• Virion structure Genomic RNA E GP2 GP3 GP4 GP5 M N

Once upon a time…

LDV

swLDV

Going wild & domestic (60-70ies)

swLDV genotype 1

genotype 2

prePRRSV

PRRSV

PRRSV

The big escape east & west in the 80’ies 1989

swLDV genotype 1

G2 (VR2332like) G1s1 (LVlike) - short fever - reproductive - listlessness problems - respiratory problems - reproductive problems

≠

PRRSV

genotype 2

prePRRSV

PRRSV

Target: Sn+CD163+ macrophage

PRRSV (G1s1;;LV) Start of replication/entry

lnn

Low transmission power

lungs cell-free viremia

lungs spleen lnn

No general/respiratory problems (≠ VR2332) Reproductive problems reactivation

persistence

1

2

3

4

5

6

7

8

9

10

11

12

Weeks pi

PRRSV (G1s1;;LV) Resp Apoptosis in infected cells & neighbouring cells

lungs

1s12010

1s1990 1

2

3

4

5

Weeks pi

PRRSV (G1s1;;LV) Resp 0 DPI

Young monocytes

Sia+ mø

Overlay

9 DPI

lungs No respiratory problems 30 DPI

Lungs

1

2

3

4

5

Weeks pi

PRRSV (G1s1;;LV) Resp 0 DPI

Young monocytes

Sia+ mø

Overlay

9 DPI

lungs Respiratory problems 30 DPI

+ other respiratory pathogens/toxins • other virus (PCV2, SIV, PRCV, ADV) • bacteria (Mycoplasma, Streptococcus, Bordetella, Salmonella) • LPS

PRRSV (G1s1;;LV) Repro

Viremia (cell-free)

PRRSV (G1s1;;LV)

80-90 days of gestation

Repro Fetal placenta


Endometrium


PRRSV (G1s1;;LV)




Endometrium


PRRSV (G1s1;;LV)




Placenta necrosis -> anoxia foetus

Endometrium

PRRSV (G1s1;;LV)


Repro

Late abortion, early farrowing Stillborn, weakborn piglets

The genetic clock is ticking - 90ies

genotype 1

G2-SAMS G2-Atypical PRRS

Fever & general disease + Respiratory problems + Secondary infections + Reproductive problems

genotype 2

The genetic clock is ticking and ticking - 00ies

G1s3-Lena genotype 1

Fever & general disease +++ Respiratory problems ++ Secondary infections +++ Reproductive problems

genotype 2

G2-HFDV

Target1: Sn+CD163+ macrophage

PRRSV (1s3;;Lena)

Target2: X+CD163+ macrophage

High transmission power

lnn lungs

Whole respiratory tract spleen lnn

cell-free viremia

reactivation

persistence

1

2

3

4

5

6

7

8

9

10

11

12

Weeks pi

Quantification of PRRSV infected cells LV

Lena

Target 2: new monocytic cell types (nasal mø)


Target 1: Sn+CD163+ macrophage

Full destruction of the first defense by mø !!!

Quantification of PRRSV infected cells

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Pig 1

Pig 2

Pig 3

Mean Nasal mucosa

Body temperature

†

†††

Respiratory distress

†

†††

≠ LV = high fever disease

The genetic clock is ticking & ticking & ticking…

genotype 1

G1s1-Flanders13

Fever & general disease + Respiratory problems + Secondary infections + Reproductive problems

genotype 2

Replication in nasal mø Target1: Sn+CD163+ macrophage Target2: X+CD163+ macrophage Cells/mm2

60

40

20

LV ‘90

?

Flandres ‘07 Genotype 1 subtype 1

Flandres ’13

Lena ’06 Genotype 1 subtype 3

VR2332 ’90

MN-184 ’01 Genotype 2

Vietnam ’13

?

Gilts

PRRSV transmission

! 40-100 kgs

10-20 kgs

Sows

√

!

! Sows+ offspring

!

20-40 kgs

! !

PRRSV transmission

Infected

Uninfected

R>1, but low (slow spread) G1s1 (old LV-like PRRSV) at low pressure of infectivity

10-20 kg

Mainly subclinical infections Acceptable problems (low percentage of animals)

20-40 kg PRRSV Virus a Virus b Bacteria c Bacteria d

Age

PRRSV transmission

Infected

Uninfected

R>>>>>1 (strong spread) 1° G1s1 (old LV-like PRRSV) at high pressure of infectivity (viremic pigs) 2° G1s1new/G1s3(Lena) (nose/tonsil/lung+)

10-20 kg

Clinical PRRSV/abcd infections

!

PRRSV Virus a Virus b Bacteria c Bacteria d

Age

PRRSV type 1 vaccination in Europe Hans Nauwynck



PRRSV-host immune response

PRRSV-host immune response 3dpi

IFNa NK

±

-


IFNa NK

±

-


IFNa NK

± ±

--


IFNa NK

± ± ±

---


non- Abies neutral.

+ neutral. - Tc -


non- Abies neutral.

++++++++++ neutral. ----------------- Tc -----------------

PRRSV-host immune response 28-35dpi

non- Abies neutral.

++++++++++++++++ neutral. -----------------------+++ Tc ---------------------------- X +++

PRRSV(LV) to which regions are antibodies directed?

E GP2a

• 0 linear antigenic regions

• 5 linear antigenic regions (1-2/17) -> 2 neutralizing

GP3


GP4

• 2 linear antigenic regions (17/17) -> 1 neutralizing

PRRSV(LV) to which regions are antibodies directed?

M

GP5



PRRSV-infected autologous target mø

PRRSV-infected heterologous target mø

PRV-infected autologous target mø

Percentage lysis of infected target macrophages (mø)

PRRSV(LV)

PRRSV-infected + MHCI-blocked autologous target mø

Effector PBMC of PRRSV-infected pigs

Effector PBMC of PRV-infected pigs

CMI PRV-infected autologous target mø

PRV-infected heterologous target mø

PRRSV-infected autologous target mø

PRV-infected + MHCI-blocked autologous target mø

PRRSV-host immune response 28-35dpi

non- Abies neutral.

++++++++++++++++ neutral. -----------------------+++ Tc ---------------------------- X +++

Infection immunity protects 100% upon re-exposure

PRRSV type 1 (European type) subtypes 1, 2, 3 & 4 type 2 (American type)

Genetic drift -> differences in virulence & pathogenicity -> effect on vaccine efficacy?

ORF5

ORF7

Vaccination with old LV-like attenuated vaccines homologous challenge

Not vaccinated 6 wks

Viremia

LVlikeAtt® 6 wks

PRRSV LV

Vaccination with old LV-like attenuated vaccines homologous challenge Not vaccinated LVlikeAtt® Vaccinated

log10 TCID50/ml serum

4

3

2

1

0 0

3

Strong protection Nabs + Cell x +

7

10

14

21

Days post challenge

Vaccination with old LV-like attenuated vaccines heterologous challenge

Not vaccinated 6wks

Viremia

LVlikeAtt® 6wks

PRRSV heterologous

Vaccination with old LV-like attenuated vaccines heterologous challenge 4

Not vaccinated log10 TCID50/ml serum

Vaccinated LVlikeAtt® 3

2

1

0 0

3

7

10

Partial protection, but still very efficient Nabs - Cell x +

14

21

Days post challenge

Vaccination with more recent attenuated vaccines homologous challenge


Viremia

PRRSV1s1-2008Att 6 wks

PRRSV08

Vaccination with more recent attenuated vaccines homologous challenge 4

Not vaccinated


PRRSV1s1-2008Att 3

2

1

0 0

Full protection Nabs + Cell x +

3

7

10

14

21

Days post challenge

Vaccination with more recent attenuated vaccines homologous challenge


PRRSV1s3LenaAtt

Viremia

6 wks

PRRSV1s3Lena

Vaccination with more recent attenuated vaccines homologous challenge Not vaccinated PRRSV1s3LenaAtt


4

3

2

1

0 0

Full protection Nabs + Cell x +

3

7

10

14

21

Days post challenge

Vaccination with experimental inactivated vaccine homologous challenge

Not vaccinated

Not vaccinated

4 wks

4 wks

Viremia

PRRSV1s1xIn

PRRSV1s1xIn 4 wks

4 wks

PRRSV1s1x

Vaccination with experimental inactivated vaccine homologous challenge 4

Not vaccinated log10 TCID50/ml serum

PRRSV1s1xIn 3

2

1

0 0

3

7

10

14

21

Days post challenge

Less efficient for primo-vaccination than attenuated vaccines Boost effect?

Gilts

Attenuated vaccine

Sows

40-100 kgs

10-20 kgs

√

How to boost? Presence of active immunity

Sows+ offspring

Neg AI-centres

20-40 kgs

Boost vaccination with different PRRSV vaccines in the presence of active immunity Serological response (SN ab titers) Not vaccinated

AutoInact

Type1Inact®

Type2att®

Type1att®

SN antibody response

Boost vaccination with different PRRSV vaccines Serological response (SN ab titers) 1024

SN titer

64

16

Not vaccinated AutoInact Type1Inact® Type2att® Type1att®

4

0 0

7

14

21

Days post vaccination

• Autogenous inactivated vaccine boosts the humoral immunity of the sow -> boosts the colostral immunity -> protection of newborn