Antibiotic-free Megatrend & New Vaccination Solutions · PDF fileAntibiotic-free Megatrend...

Marcelo PANIAGODirector Global Veterinary Services - Poultry

Ceva Santé AnimaleLibourne - France

Antibiotic-free Megatrend & New Vaccination SolutionsBarcelona, Spain – March 14th - 16th, 2016

Evolution of the poultry industry ...

www.poultry.allotment.org.uk www.engormix.com

The poultry industry is changing extremely quickly and it has brought new challenges to producers.

Evolution of the poultry industry ...Larger production complexes.

Sources: http://ian.umces.edu; http://www.poultryhub.org; http://www.airphotona.com

Evolution of the poultry industry ...Higher stocking density.

Conventionalhouses

Environmental controlled houses Broilers in cages

22 to 30 kg/m2 34 to 43 kg/m2 Up to 50 kg/m2 in each level

Four-tier cage 200 kg/m2

Evolution of the poultry industry ...Farms located in very densely populated areas.

Source: Ritter, G.D. Field Experiences with Newcastle Vector Vaccines in the USA. New Vaccine Technology Symposium, Miami, April 9th to 11th, 2013.

Evolution of the poultry industry ...Disparity in biosecurity procedures.

Evolution of the poultry industry ...Industry moving to areas with high disease pressure.

Evolution of the poultry industry ...Labor scarcity (poorly qualified farm workers).

Evolution of the poultry industry ...Consumers’ pressure to reduce the use of antibiotics and improve the welfare of the chickens.

Source: http://sheltons.com; http://www.animalwelfareapproved.org/

... evolution of the vaccinesWithin this new context, new technology vaccines will help to overcome these challenges.

More efficacious and safer vaccines;Long duration of immunity;Applied in the hatcheries;Able to reduce the shedding of the pathogens;Able to reduce the workload in the farms;Cost-effective;Etc.

New technology vaccines ...New technology vaccines

Vector vaccinesImmune complex vaccinesVector “cassete” vaccinesSub-unit vaccinesGene-deleted vaccinesReverse genetic vaccines Etc

... and their effect on sheddingNew technology vaccines

Vector vaccinesImmune complex vaccinesVector “cassete” vaccinesSub-unit vaccinesGene-deleted vaccinesReverse genetic vaccines Etc

Materials and methods

Source: Palya et al. Advancement in vaccination against Newcastle Disease: Recombinant HVT NDV provides high clinical protection and reduces challenge virus shedding with the absence of vaccine reaction. Avian Diseases, 56:282–287, 2012.

Commercial broilers (HI titer against NDV of 7.13 log2)

Clinical protection was assessed after each challenge;Oropharyngeal and cloacal swabs were taken

3 and 7 days post challengeVirus quantification using RT-PCR

Group Vaccine Age and route Challenge(Days 20 / 27 / 40)

1 rHVT-F vaccine Day of age, SQ 105.0 EID50 Chimalhuacan NDV strain (Genotype V) at 20 (CH1), 27 (CH2) and 40 (CH3) days of age by IN + ON route2 - -

Clinical protection

0 0 00

20

40

60

80

100

CH1 - D20 CH2 - D27 CH3 - D40

Mea

nof

cha

lleng

e vi

rus a

mou

nt(lo

g 10E

ID50

/ml)

Clinical protection

rHVT-F vaccine

Control

Challenge virus shedding

0123456789

Oroph swab

Cloacal swab

Oroph swab

Cloacal swab

Mea

nof

cha

lleng

e vi

rus a

mou

nt(lo

g 10E

ID50

/ml)

Reduction of sheddingChallenge at D27

rHVT-F vaccine

Control

CH2 D3 CH2 D7

~4 log10

Challenge virus shedding

0123456789

Oroph swab

Cloacal swab

Oroph swab

Cloacal swab

Mea

nof

cha

lleng

e vi

rus a

mou

nt(lo

g 10E

ID50

/ml)

Reduction of sheddingChallenge at D40

rHVT-F vaccine

Control

CH3 D3 CH3 D7

~7 log10

Materials and methodsSPF birdsVaccinated at day of age with either a rHVT-F vaccine or a concentrated inactivated ND vaccine by SQ route.

Herts 33/56 (genotype IV);D516/1/05/MX (genotype V);D1598/1/11/PH (genotype VIIa);D575/6/05/PE (genotype VIIb);D1500/2/1/10/CN (genotype VIId);D1435/3/3/SA/10 (genotype VIId);RB Daagstam ND/01/ZA (genotype VIII).

Challenge at 28 days of age by IN route with 5.0 log10 ELD50/ chicken. Clinical protection and re-excretion of challenge virus were assessed.

Source: Ceva Animal Health internal study – unpublished references: SCI-069-2011, Ceva-Phylaxia, Budapest-Hungary, 2011

Clinical protection

0 0 0 0 0 0 00

20

40

60

80

100

Herts (IV) MX (V) PH (VIIa) PE (VIIb) CN (VIId) SA (VIId) ZA (VIII)

% o

f clin

ical

pro

tect

ion

Challenge isolates

Clinical protection

rHVT-F vaccine Killed vaccine Control

Oro-nasal shedding

0,00,01,02,03,04,05,06,07,0

Herts (IV) MX (V) PH (VIIa) PE (VIIb) CN (VIId) SA (VIId) ZA (VIII)Titr

e eq

uiva

lent

unit

(log 1

0EI

D 50)

Excretion of challenge virus2 days post-challenge (oro-nasal)

rHVT-F vaccine Killed vaccine Control

Oro-nasal shedding

0,00,01,02,03,04,05,06,07,0

Herts (IV) MX (V) PH (VIIa) PE (VIIb) CN (VIId) SA (VIId) ZA (VIII) AVGTitr

e eq

uiva

lent

unit

(log 1

0EI

D 50)

Excretion of challenge virus2 days post-challenge (oro-nasal)

rHVT-F vaccine Killed vaccine Control

~1.8 log10

(~60 timesless virus)

~3.1 log10

(>1000 times less virus)

Cloacal shedding

0,0 0 0 0 0,00,0 00,01,02,03,04,05,06,07,08,0

Herts (IV) MX (V) PH (VIIa) PE (VIIb) CN (VIId) SA (VIId) ZA (VIII)Titr

e eq

uiva

lent

unit

(log 1

0EI

D 50)

Excretion of challenge virus4 days post-challenge (cloacal)

rHVT-F vaccine Killed vaccine Control

NT

Cloacal shedding

0,0 0 0 0 0,000,01,02,03,04,05,06,07,08,0

Herts (IV) MX (V) PH (VIIa) PE (VIIb) CN (VIId) SA (VIId) ZA (VIII) AVGTitr

e eq

uiva

lent

unit

(log 1

0EI

D 50)

Excretion of challenge virus4 days post-challenge (cloacal)

rHVT-F vaccine Killed vaccine Control

~0.6 log10

~6.0 log10

(~1million times less

virus)NT

Materials and methods

Source: Ceva Animal Health - Unpublished study, SSIU-Phylaxia, Budapest, Hungary

Commercial broilers (Cobb 500)

Clinical protection and virus excretion from oro-pharyngeal and cloacal swabs taken at 4 and 7 dpc were assessed.

GroupVaccination program

Challenges(21, 28 & 35 days)First vaccination

(Day-old)Second vaccination

(Day 18)

1rHVT-F vaccine (SQ) +Live attenuated ND / IB vaccine (Spray)

-Challenge with South-African “Goose Paramyxovirus” (Gen. VII) Strain2 Live attenuated ND / IB

vaccine (Spray)Live attenuated ND

vaccine (DW)3 - -

Clinical protection

0 0 00

20

40

60

80

100

rHVT-F + live ND vaccine Live ND program Control

% o

f pro

tect

ion

Clinical protection against vNDV challenge

21 days28 days35 days

Challenge virus shedding

001234567

rHVT-F + live ND vaccine Live ND program ControlTitr

eeq

uiva

lent

uni

t (lo

g 10EI

D50

/0.2

ml)

Shedding of challenge virus4 dpch – oropharyngeal swabs

21 days28 days35 days

~ 2.5 log10

Challenge virus shedding

001234567

rHVT-F + live ND vaccine Live ND program ControlTitr

eeq

uiva

lent

uni

t (lo

g 10EI

D50

/0.2

ml)

Shedding of challenge virus4 dpch – oropharyngeal swabs

21 days28 days35 days ~ 5.0 log10

Materials and methods

Source: Palya et al. Onset and long-term duration of immunity provided by a single vaccination with a turkey herpesvirus vector ND vaccine in commercial layers. Veterinary Immunology and Immunopathology 158, 105–115, 2014.

Commercial laying pullets (Lohmann brown).

Monitoring parameters (during 14 days): Daily observations for NDV specific clinical signs, mortality and virus shedding.

Group Vaccine Age and routeChallenge

(Weeks 3 / 4 / 6 / 10 / 15 / 25 / 33 / 40 / 55 / 72)

1 rHVT-F vaccine Day of age, SQ Challenge with a Genotype VII strain (Malaysian isolate)5.0 log10 EID50/bird by intranasal route.2 - -

Clinical protection

0 0 0 0 0 0 0 0 00

20

40

60

80

100

W3 W4 W6 W10 W15 W25 W33 W40 W55 W72

% o

f clin

ical

pro

tect

ion

Challenge isolates

Clinical protection

rHVT-F vaccine Control

Challenge virus shedding

3 weeks 4 weeks 6 weeks 10 weeks

~1 log10 ~2 log10 ~3 log10 ~3 log10

Challenge virus shedding

40 weeks 55 weeks 72 weeks

~3 log10

Post-vaccination reactions

Comparison: Three (3) consecutive years: (light broilers)

Period* VaccineProdutictive Parameters

Age (days) Mortality (%) BW (g) FCR EEI % Condenation

2007-08 Conventional 40.7 4.4 2018 1.81 262 0.63

2008-09 Vector HVT-F 39.0 2.8 2068 1.76 293 0.23

2009-10 Vector HVT-F 38.2 2.6 2028 1.73 299 0.12

Source: Holder, T. Field Experience with HVT Vector Newcastle Vaccines. Presentation at Vector Vaccines Symposium – San Diego –USA, 2010. Available at www.vector-vaccines.com

* August to July

Post-vaccination reactions

Comparison: Three (3) consecutive years: (light broilers)

Period* VaccineProdutictive Parameters

Age (days) Mortality (%) BW (g) FCR EEI % Condenation

2007-08 Conventional 40.7 4.4 2018 1.81 262 0.63

2008-09 Vector rHVT-F 39.0 2.8 2068 1.76 293 0.23

2009-10 Vector HVT-F 38.2 2.6 2028 1.73 299 0.12* August to July

Source: Holder, T. Field Experience with HVT Vector Newcastle Vaccines. Presentation at Vector Vaccines Symposium – San Diego –USA, 2010. Available at www.vector-vaccines.com

Post-vaccination reactions

Comparison: Three (3) consecutive years: (light broilers)

Period* VaccineProdutictive Parameters

Age (days) Mortality (%) BW (g) FCR EEI % Condenation

2007-08 Conventional 40.7 4.4 2018 1.81 262 0.63

2008-09 Vector rHVT-F 39.0 2.8 2068 1.76 293 0.23

2009-10 Vector rHVT-F 38.2 2.6 2028 1.73 299 0.12* August to July

Source: Holder, T. Field Experience with HVT Vector Newcastle Vaccines. Presentation at Vector Vaccines Symposium – San Diego –USA, 2010. Available at www.vector-vaccines.com

Materials and methodsSPF chickens.

Clinical protection was evaluated.Collection of swabs (RRT-PCR) at 2, 4, 6 and 8 dpi to assess the reduction of shedding.

Group Vaccine Age and route Challenge(4 weeks)

1 rHVT-H5 Day of age, SQ HPAIV H5N1 A/chicken/Bangladesh/11RS1984-33/2011 Clade 2.3.2.1

at 106 EID50/0.1ml per bird 2 - Day of age, SQ

Source: Bonfante et al. Efficacy of a single dose of rHVT-H5 Avian Influenza vector vaccine against a clade 2.3.2.1 of H5N1 Highly Pathogenic virus, Proceedings of the WVPA Congress – Nantes, France, 19-23 August 2013

Clinical protection

00

20

40

60

80

100

rHVT-H5 vaccine Control

% p

rote

ctio

nClinical protection after challenge

Shedding

Shedding was detected in only 20% of the vaccinated and challenged chickens.

CS=cloacal swab; CSS=choanal slit swab

Materials and methods

Source: Kapczynski et al. Vaccine protection of chickens against antigenically diverse H5 highly pathogenic avian influenza isolates with a live HVT vector vaccine expressing the influenza hemagglutinin gene derived from a clade 2.2 avian influenza virus . Vaccine 33 ,1197–1205, 2015.

SPF birds (white leghorn).

Following challenge, groups were monitored twice daily for 14 days for clinical signs and mortalityOro-pharyngeal and cloacal swab samples were collected on days 2 and 4 post-challenge for virus isolation.

Group Vaccine Age and route Challenge(W6)

1 rHVT-H5 vaccine Day of age, SQ HPAI SM05 H5N1clade 2.2 virus at 106 EID50 perchicken by intra-nasal route

(homologous challenge)2 Vaccine diluent Day of age, SQ

Clinical protection

00

20

40

60

80

100

rHVT-H5 vaccine Control

% p

rote

ctio

nClinical protection after challenge

Shedding

0 0 00

20

40

60

80

100

Oroph swab Cloacal swab Oroph swab Cloacal swab

% o

f pos

itive

bird

sPercentage of sheddres

rHVT-H5

Control~85%

2 dpch 4 dpch

ND ND

SheddingOropharyngeal swabs (2 dpch).

6 log10

SheddingCloacal swabs (2 dpch).

~3.5 log10

Materials and methods

Source: Rauw et al. Efficacy of rHVT-AI vector vaccine in broilers with passive immunity against challenge with two antigenically divergent Egyptian clade 2.2.1 HPAI H5N1 strains . Avian Diseases 56:913–922, 2012.

Commercial Hubbard F15-type broiler chickens with and without MDAAIV(H5N1)

GroupVaccination

Challenge (4 weeks)Vaccine Age (days)

Negative (MDA -) None - H5N1 Egypt 2008

(A/Chicken/Egypt/1709-6/2008 strain, clade

2.2.1).

Chickens were challenged by the oculonasal route with 106

EID50 of HPAI H5N1 virus

Negative (MDA+) None -rHVT-H5 (MDA -) rHVT-H5 1rHVT-H5 (MDA +) rHVT-H5 1Inact H5N1 (MDA -) Inact H5N1 10Inact H5N1 (MDA +) Inact H5N1 10

rHVT-H5/Inact H5N1 (MDA -)rHVT-H5 1Inact H5N1 10

rHVT-H5/Inact H5N1 (MDA -)rHVT-H5 1Inact H5N1 10

Clinical protection

0

20

40

60

80

100

None (MDA-)

None (MDA+)

rHVT-H5 (MDA-)

rHVT-H5 (MDA+)

Inact (MDA-)

Inact (MDA+)

rHVT-H5 & Inact

(MDA-)

rHVT-H5 & Inact

(MDA+)

% p

rote

ctio

n

Clinical protection

Percentage of shedders

0 0 0 0 00

20

40

60

80

100

None (MDA-)

None (MDA+)

rHVT-H5 (MDA-)

rHVT-H5 (MDA+)

Inact (MDA-)

Inact (MDA+)

rHVT-H5 & Inact

(MDA-)

rHVT-H5 & Inact

(MDA+)

% o

f she

dder

s

Percentage of shedders- Oropharyngeal swabs -

2 dpch4 dpch7 dpch

SM. Specific mortality

SM SM SM

Percentage of shedders

00

20406080

100

rHVT-H5 (MDA-) rHVT-H5 (MDA+) Inact (MDA-) Inact (MDA+)

% o

f she

dder

s

Percentage of shedders- Oropharyngeal swabs -

2 dpch4 dpch7 dpch

Comparison of the groups of birds vaccinated with rHVT-H5 and inactivated vaccines.

~60%

Challenge virus shedding

00,01,02,03,04,05,0

rHVT-H5 (MDA-) rHVT-H5 (MDA+) Inact (MDA-) Inact (MDA+)

Mat

rix g

ene

copi

es in

m

illili

ters

of s

wab

s (lo

g 10)

Challenge virus shedding- Oropharyngeal swabs -

2 dpch4 dpch7 dpch

~ 2.5 log10

Comparison of the groups of birds vaccinated with rHVT-H5 and inactivated vaccines.

Materials and methods

Source: Kilanyet al. Evaluation of four different vaccination programs against HPAI 2011 Egyptian virus in commercial broiler chickens reared under laboratory conditions. 63rd WPDC/XXXIX ANECA 2 – 5 April 2014, Puerto Vallarta, Jalisco, México

Commercial broilers with MDAAIV(H5N1)

Clinical protection and virus excretion by real time RT-PCR from oro-pharyngeal swabs taken at 3, 6, 10 and 14 dpc were assessed.

GroupVaccination program Challenge

(29 days)Vaccine Age (days)1 rHVT-H5 1 HPAIV H5N1 variant clade 2.2.1.1

(A/Chicken/Egypt/116AD/2011).administered at a dose of 106

EID50/bird given via intra-nasal route.

2 Inactivated vaccine - H5N1 RG 73 Inactivated vaccine - H5N2 74 Inactivated vaccine - H5N3 RG 75 - -6 - -

Clinical protection

0

20

40

60

80

100

rHVT-H5 H5N1 RG H5N2 H5N3 RG Positive control Negative control

% p

rote

ctio

n

Clinical protection

Virus shedding

0

20

40

60

80

100

rHVT-H5 H5N1 RG H5N2 H5N3 RG Positive control

% o

f bird

s

Percentage of shedder birds- Oropharyngeal swabs -

3 dpch6 dpch

~50% ~55% ~30% ~75%

ConclusionsThe poultry industry is changing extremely quickly and it has brought new challenges to producers;

Within this environment, much more is expected from vaccines;

New technology vaccines such as rHVT-based vector vaccines against ND and AI induce better clinical protection and reduced significantly the number of shedders and amount of virus shed when compared to live and/or inactivated vaccines;

Vector HVT-F vaccine stops the circulation of live attenuated ND vaccines hence reducing the post vaccination reactions.

marcelo.paniago@ceva.com

Antibiotic-free Megatrend & New Vaccination SolutionsBarcelona, Spain – March 14th - 16th, 2016