In vivo evaluation of Lumpy Skin Disease vaccine efficacy in - - PowerPoint PPT Presentation

in vivo evaluation of lumpy skin disease vaccine efficacy
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In vivo evaluation of Lumpy Skin Disease vaccine efficacy in - - PowerPoint PPT Presentation

In vivo evaluation of Lumpy Skin Disease vaccine efficacy in controlled environment Andy Haegeman, Laurent Mostin, Maria Vastag, Willem Van Campe, Nadav Galon, Estelle Venter, Annebel De Vleeschauwer, Eeva Tuppurainen, Kris De Clercq


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SLIDE 1

In vivo evaluation

  • f Lumpy Skin

Disease vaccine efficacy in controlled environment

31/ 01/ 2017

Andy Haegeman, Laurent Mostin, Maria Vastag, Willem Van Campe, Nadav Galon, Estelle Venter, Annebel De Vleeschauwer, Eeva Tuppurainen, Kris De Clercq

European Medicines Agency

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SLIDE 2
  • Infection route:
  • Intravenously
  • Intra-dermal: 4 sites, 2 on each side of the neck
  • Infection dose:
  • 105.4-6 TCID50/ 100 µl
  • Number of animals per group: N = 8
  • Clinical scoring (21 days) includes:
  • Body temperature, Lnn swelling, nodule development

(number and size), feed uptake, conjunctivitis, general behaviour, local reaction (vaccination and challenge sites)

  • Sampling
  • EDTA blood, buccal swabs: PCR, Virus isolation
  • Bopsies, tissues and organs: PCR , Virus isolation
  • Serum: IPMA and virusneutralisation test
  • Heparinized blood: IFN release

2

LSDV: I nfection Model

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SLIDE 3
  • Some data of the comparison: Sim ilarities
  • Body temperatures:

 Both show a fever spike around 7/ 8 dpi. Prolonged fever period can occur (app. 25% for both)

3

LSDV: I nfection Model

Neethling strain Vs a field isolate from Israel

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SLIDE 4
  • Some data of the comparison: Sim ilarities
  • Seroconversion

4

LSDV: Infection Model

Neethling strain Vs a field isolate from Israel

Onset : 4 to 13 dpi (both)  a tendency to have more Abs with Neethling

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SLIDE 5

1 2 3 4 5 6 7 8 9 10

  • 6
  • 5
  • 4
  • 3
  • 2
  • 1

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

  • Some data of the comparison: differences
  • Clinical signs after challenge Number of nodules /

generalisation / clinical scores

2/02/2017 5

LSDV: Infection Model

Neethling strain Vs a field isolate from Israel

Neethling strain Field isolate from Israel

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SLIDE 6
  • Some data of the comparison: differences
  • Virus detection in blood: detection as early as 2/ 3 dpi for
  • both. But vireamic period is longer and viral load in general

higher with field isolate from Israel

2/02/2017 6

LSDV: Infection Model

Neethling strain Vs a field isolate from Israel

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SLIDE 7

7

° IFNg release upon stimulation in vitro: Much low er IFNg release in animals infected with the Israeli field isolate.

Israeli isolate Neethling strain

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SLIDE 8
  • Some data of the comparison: Conclusion

When all data was analysed the Israeli field isolate is more interesting to be used for our vaccine trials.

8

LSDV: Infection Model

Neethling strain Vs a field isolate from Israel

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SLIDE 9
  • Com m ercial available  Live attenuated vaccines ( LAV)
  • Sheeppox based (RM-65)

 JoviVac (Jordan Bio-Industries Center (JOVAC); Jordan)  Abic (Abic Biological Laboratories Ltd (Phibro); Israel)  Penpox (Pendink Institute; Turkey)

  • LSDV-based

 OBP (Onderste Poort; South-Africa)  LumpyVax (MSD; South-Africa)  HerbiVac (Deltamune, South-Africa)

  • Goatpox based

 CapriVac (Jordan Bio-Industries Center (JOVAC); Jordan)

  • Sheep and goatpox based or LSDV?(Cfr Tuppurainen et al., 2014)

 KSGP 0240/ 0180 (Jordan Bio-Industries Center (JOVAC); Jordan)

  • New I nactivated Vaccine ( MCI , Morocco)
  • Sheeppox-based
  • LSDV-based

9

LSDV: Vaccine trials

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SLIDE 10
  • Num ber of anim als:
  • 7 animals per vaccine group
  • 5 control animals (not vaccinated)
  • Vaccination: as described by com pany
  • Single vaccination
  • Challenge: 2 1 days after vaccination
  • Sam pling and follow -up: as described for m odel

10

LSDV: Vaccine trial set-up

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SLIDE 11
  • Trials and analyzes are still ongoing, some prelim inary

results:

  • Limited side effects were seen for some vaccines:

 Elevated temperatures around 7/ 8 dpv (time point similar to

the 7/ 8 dpi fever spike after infection)

11

LSDV Vaccine trials:

prelim inary results

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SLIDE 12

0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Dpi

Averaged local reaction

LAV2 LAV3 Lav4

  • Clinical signs
  • None (for example LAV2, LAV3)
  • Nodule formation (onset 7-> 9 dpi; similar to control group)

(for example LAV4)

  • Local reaction at inoculation site
  • Transiently (LAV2, LAV3)
  • Continued (LAV4)

12

LSDV Vaccine trials:

preliminary results

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SLIDE 13
  • Viremia following challenge:
  • Completely blocked  Strong Vaccine effect (LAV2)
  • Almost completely blocked Vaccine effect (LAV3)

13

1 positive sampling in 1 animal

LSDV Vaccine trials:

preliminary results

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SLIDE 14
  • Viremia following challenge:
  • Completely blocked  Strong Vaccine effect
  • All most completely blocked  Vaccine effect
  • No blocking  No Vaccine effect (LAV4)

14

LSDV Vaccine trials:

preliminary results

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SLIDE 15
  • Serological response:
  • Strong

 Early detection  At moment of challenge:

  • 100% seroconverted
  • Some moderate to strong positive

15

LSDV Vaccine trials:

preliminary results

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SLIDE 16
  • Serological response:
  • Moderate

 Starts later  At moment of challenge:

  • Not 100% seroconverted but the majority
  • Some moderate positive

16

LSDV Vaccine trials:

preliminary results

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SLIDE 17
  • Serological response:
  • W eak

 Starts later  At moment of challenge:

  • Minority was seroconverted
  • Only weak positive

17

LSDV Vaccine trials:

preliminary results

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SLIDE 18
  • IFNgamma release upon stimulation:
  • Strong

18

LSDV Vaccine trials:

preliminary results

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SLIDE 19
  • IFNgamma release upon stimulation:
  • Moderate

19

LSDV Vaccine trials:

preliminary results

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SLIDE 20
  • IFNgamma release upon stimulation:
  • W eak

20

LSDV Vaccine trials:

preliminary results

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SLIDE 21
  • Virus distribution in organs/ tissues
  • None or very lim ited and with very low viral load (LAV2 and 3)

21

LSDV Vaccine trials:

preliminary results

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SLIDE 22
  • Virus distribution in organs/ tissues
  • Broad distribution pattern (LAV4)

22

LSDV Vaccine trials:

preliminary results

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SLIDE 23

The LSD challenge model allows the identification of:

  • Vaccines with very good potential
  • No viremia, elicits high Abs response and good IFNg release, almost

no traces of viral DNA found in organs

  • Although very slight side effects after vaccination (fever)
  • Vaccines with good potential
  • Almost no viremia, elicts good Abs and IFNg response , almost no

traces of viral DNA found in organs

  • Vaccines (partially) failing to protect the animals
  • Strong viremia, Low Abs and IFNg response, virus widely spread in

the organs. Animals in this groups also secreted the virus as detected by buccal swabs.

  • None of the LAV vaccines protected against the initial fever spike !
  • Inactivated vaccines: booster vaccination needed; promising results after
  • ne vaccination.

23

LSDV Vaccine trials: First conclusions

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SLIDE 24

24

Acknowledgements

  • Dr Eeva Tuppurainen
  • Prof. E. Venter (S-Africa)
  • Colleagues from Israel