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