New technology vaccines compatibility Yannick Gardin, · New technology vaccines compatibility...

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New technology

vaccines compatibility

Yannick Gardin,Innovation & Strategy Biology

Director, Ceva Group, France

Introduction

EFFICACY

SAFETY

COMPATIBILITY

Introduction

EFFICACY

SAFETY

COMPATIBILITY

What has changed ?

Huge opportunities from Biotechnology

Vaccination is routine tool of Production

Production & Process > Science

What has changed ?

Huge opportunities from Biotechnology

Vaccination is routine tool of Production

Production & Process > Science

Biotechnology ?

Biotechnology ?

LIVE

ATTENUATED

Biotechnology ?

INACTIVATED

ADJUVANTED

LIVE

ATTENUATED

Biotechnology ?

Biotechnology ?

Epitope

(virulence / protection)

Biotechnology ?

Epitope

(virulence / protection)

Genome

(gene / deletion / insertion)

Biotechnology ?

Carrier

(expression / virulence)

Epitope

(virulence / protection)

Genome

(gene / deletion / insertion)

Biotechnology ?

Antibody

(immune-complex)

Epitope

(virulence / protection)

Genome

(gene / deletion / insertion)

Carrier

(expression / virulence)

Biotechnology ?

Subunit VectorReverse genetics

Immunecomplex

Etc.

Antibody

(immune-complex)

Epitope

(virulence / protection)

Genome

(gene / deletion / insertion)

Carrier

(expression / virulence)

What has changed ?

Huge opportunities from Biotechnology

Vaccination is routine tool of Production

Production & Process > Science

What has changed ?

Huge opportunities from Biotechnology

Vaccination is routine tool of Production

Production & Process > Science

Production & Process > Science

Production & Process > Science

Production & Process > Science

HATCH

Production & Process > Science

HATCH

Production & Process > Science

HATCH TRANSFER

Production & Process > Science

IBD IB

SHS MDND

COCCI

CAMPY AI(H9)

AI(H5)

ILT

SALMO

IBvar.

etc.

AI(H7)

ALL IN ONE

Production & Process > Science

ALL IN ONE

means

Production & Process > Science

EFFICACY

SAFETY

COMPATIBILITY

ALL IN ONE

means

Production & Process > Science

EFFICACY

SAFETY

COMPATIBILITY

Production & Process > Science

EFFICACY

SAFETY

Production & Process > Science

COMPATIBILITY

COMPATIBILITY

Compatibility ?

IBDND

Compatibility ?

IBDND

WHICH CRITERIA ?

Compatibility ?

IBDND

Compatibility ?

Be specific, not general !

Compatibility ?

Level of Immunity

Onset of Immunity

Duration of Immunity

Be specific, not general !

Compatibility ?

Interference

Addition

Synergism

Level of Immunity

Onset of Immunity

Duration of Immunity

Be specific, not general !

Compatibility ?

Interference

Addition

Synergism

Level of Immunity

Onset of Immunity

Duration of Immunity

Be specific, not general !

Significance / Consequences

10

20

30

40

50

60

70

80

90

100

Protection (%)

00 5 10 15 20 25 30 Age (days)35 40 45 50

Maternally Derived Antibodies

Live Respiratory vaccine

rHVT Vector vaccine

Immune Complex vaccine

Compatibility ?

Dynamics of Vaccine Immunity

Compatibility ?

Investigation of Vaccine Immunity variables

Protection against challenge

- various ages, strains, doses, etc.

- clinical protection (mortality,

morbidity, lesions)

- re-excretion of challenge virus

Humoral immunity / Antibody response :

- general / local / assay

Cell-mediated immunity :

- general / local / assay

INVESTIGATION RESULTS

Compatibility ?

Transmune Immune Complex IBD

Vectormune ND rHVT-ND F gene

Vectormune IBD rHVT-IBD VP2 gene

Vectormune AI rHVT-AI HA(H5) gene

Vectormune LT rHVT-LT gB gene

Compatibility ?

Immune Complex IBD (Transmune)

& rHVT-ND (Vectormune ND)

Broilers with MDA / NDV & IBDV

Detection of vaccine take :- Immune complex : PCR / bursa samples

- rHVT-ND : PCR / spleen samples

NDV challenge : 105 EID50 – Genotype VII str.

- Clinical protection

- HI antibody response

- shedding 4 & 7 dpc at 3 & 6 weeks

vvMDV challenge : RB1B at 8 days

Compatibility ?

Immune Complex IBD (Transmune)

& rHVT-ND (Vectormune ND)

Compatibility ?

DETECTION OF VACCINE TAKES

rHVT-ND

SPLEEN

10 DPV

W2512 IBDV

BURSA

28 DPV

Immune complex IBD - 90 %

rHVT-ND 100 % -

Immune Complex

+ rHVT-ND100 % 80 %

BROILERS

Immune Complex IBD (Transmune)

& rHVT-ND (Vectormune ND)

Positivity

limit

n.a. b b a b b a a a

Compatibility ?

NDV ANTIBODY RESPONSE (HI)

Immune Complex IBD (Transmune)

& rHVT-ND (Vectormune ND)

Compatibility ?

CLINICAL PROTECTION / NDV CHALLENGE

Immune Complex IBD (Transmune)

& rHVT-ND (Vectormune ND)

b b a b b a a a a a

b b a b b a a a a a

Compatibility ?

SHEDDING OF ND CHALLENGE VIRUS

Challenge at week 3 Challenge at week 6

Immune Complex IBD (Transmune)

& rHVT-ND (Vectormune ND)

82%

98%

30%

Compatibility ?

CLINICAL PROTECTION / MDV CHALLENGE

Immune Complex IBD (Transmune)

& rHVT-ND (Vectormune ND)

82%

98%

30%

Compatibility ?

CLINICAL PROTECTION / MDV CHALLENGE

Immune Complex IBD (Transmune)

& rHVT-ND (Vectormune ND)

Compatibility ?

rHVT-ND (Vectormune ND)

& rHVT-IBD (Vectormune IBD)

Compatibility ?

Broilers with MDA against NDV, Classical &

Variant E IBDV

Challenges :

- NDV : 105 EID50 – Chimalhuacan str.

- vvIBDV : 105 EID50 – TR isolate

- Variant IBDV : 105 EID50 – Del. E strain

Protection against IBDV assessed 10 dpc

rHVT-ND (Vectormune ND)

& rHVT-IBD (Vectormune IBD)

Compatibility ?

14 21 28 36

rHVT-ND

rHVT-IBD

rHVT-ND +

rHVT-IBD

Controls

% protection / NDV vvIBDV var.E IBDV challenge

BROILERS

rHVT-ND (Vectormune ND)

& rHVT-IBD (Vectormune IBD)

Compatibility ?

14 21 28 36

rHVT-ND 0 84 100 100

rHVT-IBD

rHVT-ND +

rHVT-IBD

0 37 70 70

Controls

0 0 0 0

% protection / NDV vvIBDV var.E IBDV challenge

BROILERS

rHVT-ND (Vectormune ND)

& rHVT-IBD (Vectormune IBD)

Compatibility ?

14 21 28 36

rHVT-ND 0 84 100 100

rHVT-IBDnd 30 nd 80

rHVT-ND +

rHVT-IBD

0 37 70 70

nd 10 nd 40

Controls

0 0 0 0

nd 10 nd 0

% protection / NDV vvIBDV var.E IBDV challenge

BROILERS

rHVT-ND (Vectormune ND)

& rHVT-IBD (Vectormune IBD)

Compatibility ?

14 21 28 36

rHVT-ND 0 84 100 100

rHVT-IBDnd 30 nd 80

20 60 90 80

rHVT-ND +

rHVT-IBD

0 37 70 70

nd 10 nd 40

0 10 11 40

Controls

0 0 0 0

nd 10 nd 0

0 0 0 0

% protection / NDV vvIBDV var.E IBDV challenge

BROILERS

rHVT-ND (Vectormune ND)

& rHVT-IBD (Vectormune IBD)

Compatibility ?

14 21 28 36

rHVT-ND 0 84 100 100

rHVT-IBDnd 30 nd 80

20 60 90 80

rHVT-ND +

rHVT-IBD

0 37 70 70

nd 10 nd 40

0 10 11 40

Controls

0 0 0 0

nd 10 nd 0

0 0 0 0

% protection / NDV vvIBDV var.E IBDV challenge

BROILERS

rHVT-ND (Vectormune ND)

& rHVT-IBD (Vectormune IBD)

Compatibility ?

14 21 28 36

rHVT-ND 0 84 100 100

rHVT-IBDnd 30 nd 80

20 60 90 80

rHVT-ND +

rHVT-IBD

0 37 70 70

nd 10 nd 40

0 10 11 40

Controls

0 0 0 0

nd 10 nd 0

0 0 0 0

% protection / NDV vvIBDV var.E IBDV challenge

BROILERS

rHVT-ND (Vectormune ND)

& rHVT-IBD (Vectormune IBD)

Compatibility ?

rHVT-ND (Vectormune ND)

& rHVT-LT (Vectormune LT)

Compatibility ?

Broilers

Challenges at 3 weeks PV

NDV : NDV B1 strain – Eye drop

- Re-isolation from trachea 5 dpc

ILTV : 103 EID50 – USDA challenge str.

- Clinical protection over 10 dpc

rHVT-ND (Vectormune ND)

& rHVT-LT (Vectormune LT)

Compatibility ?

ND PROTECTION%

rHVT-ND (Vectormune ND)

& rHVT-LT (Vectormune LT)

Compatibility ?

LT PROTECTION

0102030405060708090

rHVT LT rHVT LT + VTM HVT NDV

rHVT LT + VTM HVT NDV

CHALLENGE CONTROL

%

rHVT-ND (Vectormune ND)

& rHVT-LT (Vectormune LT)

Compatibility ?

LT PROTECTION

0102030405060708090

rHVT LT rHVT LT + VTM HVT NDV

rHVT LT + VTM HVT NDV

CHALLENGE CONTROL

%

rHVT-ND (Vectormune ND)

& rHVT-LT (Vectormune LT)

Compatibility ?

rHVT-ND (Vectormune ND)

& rHVT-AI (Vectormune AI)

Compatibility ?

SPF chickens

Challenges :

- NDV : 105 EID50 – Genotype VII Malaysian str.

- HPAIV : 106 EID50 – Egypt 2008 H5N1 strain

rHVT-ND (Vectormune ND)

& rHVT-AI (Vectormune AI)

Compatibility ?

28 56

rHVT-ND

rHVT-AI

rHVT-ND +

rHVT-AI

Controls

% protection / NDV HPAIV challenge

SPF

rHVT-ND (Vectormune ND)

& rHVT-AI (Vectormune AI)

Compatibility ?

28 56

rHVT-ND 100 100

rHVT-AI

rHVT-ND +

rHVT-AI

100 100

Controls0 0

% protection / NDV HPAIV challenge

SPF

rHVT-ND (Vectormune ND)

& rHVT-AI (Vectormune AI)

Compatibility ?

28 56

rHVT-ND 100 100

rHVT-AI 100 100

rHVT-ND +

rHVT-AI

100 100

100 90

Controls0 0

0 0

% protection / NDV HPAIV challenge

SPF

rHVT-ND (Vectormune ND)

& rHVT-AI (Vectormune AI)

Compatibility ?

Layer pullets with MDA / NDV & H5N1 AIV

Challenges :

- NDV : 105 EID50 – Genotype VII Malaysian str.

- HPAIV : 106 EID50 – Egypt 2008 H5N1 strain

rHVT-ND (Vectormune ND)

& rHVT-AI (Vectormune AI)

Compatibility ?

% protection / NDV HPAIV challenge

21 28 49 70

rHVT-ND

rHVT-AI

rHVT-ND +

rHVT-AI

Controls

LAYERS

rHVT-ND (Vectormune ND)

& rHVT-AI (Vectormune AI)

Compatibility ?

% protection / NDV HPAIV challenge

21 28 49 70

rHVT-ND 90 100 100 100

rHVT-AI

rHVT-ND +

rHVT-AI

85 85 95 100

Controls15 0 0 0

LAYERS

rHVT-ND (Vectormune ND)

& rHVT-AI (Vectormune AI)

Compatibility ?

21 28 49 70

rHVT-ND 90 100 100 100

rHVT-AI nd 0 100 80

rHVT-ND +

rHVT-AI

85 85 95 100

nd 20 80 90

Controls15 0 0 0

nd 0 0 0

% protection / NDV HPAIV challenge

LAYERS

rHVT-ND (Vectormune ND)

& rHVT-AI (Vectormune AI)

Compatibility ?

21 28 49 70

rHVT-ND 90 100 100 100

rHVT-AI nd 0 100 80

rHVT-ND +

rHVT-AI

85 85 95 100

nd 20 80 90

Controls15 0 0 0

nd 0 0 0

% protection / NDV HPAIV challenge

LAYERS

rHVT-ND (Vectormune ND)

& rHVT-AI (Vectormune AI)

CONCLUSIONS

Biotechnology has given us the possibility to

have chickens vaccinated against many

diseases in only one (broilers) or two (layers,

breeders) vaccination sessions : at hatch and

at transfer.

This will perfectly answer Production and

Process constraints of the poultry industry.

This described situation is stressing the

importance of Compatibility studies between

specific vaccines. General assumptions are

not advised.

Conclusions (1)

Detailed studies are needed to Investigate

various aspects of protection included in the

Compatibility concept.

Results are seldom black or white :

- they need to be discussed,

- consequences weighted,

- so that reliable, sound and clear

recommendations can be given to users

Final decision is often an acceptable

compromise and need to be adapted to

different field situations.

Conclusions (2)

According to experiments conducted to date,

we concluded to :

Compatibility between :

- Transmune & Vectormune ND

- Transmune & Vectormune FP-LT

- Vectormune ND & Vectormune AI (&

Transmune)

- Vectormune ND & Vectormune FP-LT

No compatibility between :

- Vectormune ND & Vectormune IBD

- Vectormune ND & Vectormune LT

Conclusions (3)

Regarding combination with Live & Inactivated

classical vaccines, we concluded to :

Compatibility between :

- Cevac Vitabron L (live ND & IB - given by

spray & Transmune & Vectormune range

- Cevac MD SB-1 or Cevac MD Rispens

vaccines & Vectormune (HVT) range

- Transmune & Cevac Broiler ND K

(Inactivated ND vaccine)

Conclusions (4)

MANY THANKS TO

CEVA PARTNERS

& CEVA COLLEAGUES

Vectormune ND / Vectormune AI

THANK YOU

FOR YOUR ATTENTION

Vectormune ND / Vectormune AI