Huvepharma gut health training Oct 2018 Coccidiosis control - vaccines

Introduction

• Coccidiosis control

Chemotherapy
CONTROLLING COCCIDIOSIS WITH
VACCINES
Monita Vereecken, Huvepharma NV, Belgium

Monita Vereecken, DVM Vaccination

Technical Manager Europe
Product Manager Coccidiosis Vaccines Europe

1 2

Introduction Introduction

• Coccidiosis control • Coccidiosis control

Chemotherapy Chemotherapy
Ionophores Chemicals Combination Ionophores Chemicals Combination

Vaccination Vaccination
Attenuated Non Attenuated Subunit Attenuated Non Attenuated Subunit

3 4

Vaccination? Vaccine choice? Which species?

• 7 Eimeria species in chickens
Longer living birds

Broilers

5 6

1
Huvepharma gut health training Oct 2018 Coccidiosis control - vaccines

Protection to which species? Eimeria necatrix and Eimeria brunetti

• Prevalence? • Pathogenic species

• Field: Diagnostics based on lesions • Mortality, typical lesions
• Outbreaks usually occur after 6 weeks of
age

Prevalence of species ? Mixed coccidiosis infections

• Mixed infection • Mixed infection

• Common in the field • Common in the field

Godwin and Morgan, 2015 Godwin and Morgan, 2015

10 11

Mixed coccidiosis infections Mixed coccidiosis infections

Damer Blake, 2015

The recognised
Eimeria species
are ubiquitous

At least 2 of the 3
cryptic OTU
genotypes are
Widespread
below south of
30oN

12 13

2
Huvepharma gut health training Oct 2018 Coccidiosis control - vaccines

Coccidiosis vaccines Coccidiosis vaccines

Vaccines for broilers : 3 to 5 species

Vaccines for chickens > 6 weeks: 4-8 species
(breeders/layers/slow growing broilers)
Ahmad et al., 2016

15

Coccidiosis vaccines Coccidiosis vaccines

• Live “virulent” vaccines • Europe

• Since 1952 • Attenuated vaccines
• Live “attenuated” vaccines ▪ Precocious
• EU Repeated selection of oocysts
• Methods for attenuation: with short prepatent period

▪ Heat treatment
▪ X irriadiation
▪ Passage through embryonated eggs SPF birds
▪ Selection for precocity Day 0 Day 4 Day 8

16 17

Coccidiosis vaccines Wild type versus attenuated

Wild type vaccine Attenuated vaccine

Live sporulated oocysts

Trickle vaccination (controlled Mechanism of attenuation needed

exposure + re-infection)
asexual Lower reproduction potential
replication High reproduction potential

Low pathogenic Apathogenic

Less damage
High immunogenic
Lower reproduction potential
In SPF birds
Production in conventional birds

18 19

3
Huvepharma gut health training Oct 2018 Coccidiosis control - vaccines

Key points for solid immunity Vaccine application

On feed On birds Hatchery Drinking water

In ovo

Eye drop In ovo

20 21

Eye drop Vaccine application

• Eye drop method: • 2 set of trials

• Oral application • Bioproperties
▪ Eye drops drain down to Attenuated - Huvepharma NV
the throat via
▪ Vaccine: HuveGuard® MMAT
nasolacrimal duct ▪ Eimeria maxima, E. mitis, E. acervulina, E. tenella

▪ By Swallowing the drops

oocysts enter the • Zoetis
Wild - Huvepharma Inc.
intestinal tract ▪ Vaccine: Inovocox®
▪ Eimeria maxima, E. acervulina, E. tenella

Each individual bird will be vaccinated with the correct dose!

22 23

Vaccine application Vaccine application

• Comparison of different application methods • Trial set up HuveGuard® MMAT
of HuveGuard® MMAT
• Highest value on each day = 100%
• Eye drop • Others compared to this highest value
• Spray on feed Vaccination on Day 1

• Spray on chicks • Number of birds positive is 5/5 except when

mentioned.
• Drinking water Vaccination on Day 3

24 26

4
Huvepharma gut health training Oct 2018 Coccidiosis control - vaccines

Vaccine application Vaccine application

• Results - HuveGuard® MMAT • Comparison of different application methods

of Inovocox®
Trial 1
100 100
100 89
80 • In ovo Vaccination on Day 19

60 50
6 DPV
40 4/5 4/5 4/5
• Gavage
7DPV
• Spray on chicks Vaccination on Day 1
20
4 5 5 • Gel on chicks
0.11
0
Eye drop Spray on feed Spray on bird Drinking water

27 28

Vaccine application Application methods- Conclusions

• Results- Inovocox® • Eye drop, gavage and drinking water higher

100 100 OPG’s and higher percentage of birds (in fact=
90 droppings) excreting than spray on birds,
80
70 8/8 spray on feed and in-ovo
60
50
40 • Drinking water applied in more “mature birds”
30
20 6/8 6/8 7/8 of 3 days old. Is this the reason for the
10 2.01 3.15 2.82 succesfull multiplication?
0 ▪ Drinking water in bell drinkers (trial) versus
Gavage In ovo Spray Gel
waterlines (in practice) might have different outcome

30 31

Application methods Key points for solid immunity

33

5
Huvepharma gut health training Oct 2018 Coccidiosis control - vaccines

PROPER DOSE

Allows for cycling

Vaccine application- in practice Vaccine application- in practice

36 37

6
Huvepharma gut health training Oct 2018 Coccidiosis control - vaccines

Vaccine application- in practice

41

Vaccine application- in practice Color agents

Color agent Brilliant Blue Green dye

42
Caldwell et al. , 2001

Composition of different EU coccidiosis vaccines

Visualisation
E. acervulina E. maxima E. tenella E. mitis E. praecox E. necatrix E. brunetti

HuveGuard®
Color agent Brilliant Blue Green dye Paracox® 8 x2
Evalon
Visualization of spray Tongue takes Livacox® Q

Long living broilers, breeders, layers

7
Huvepharma gut health training Oct 2018 Coccidiosis control - vaccines

Composition of different EU coccidiosis vaccines Composition of different EU coccidiosis vaccines

E. acervulina E. maxima E. tenella E. mitis E. praecox E. necatrix E. brunetti E. acervulina E. maxima E. tenella E. mitis E. praecox E. necatrix E. brunetti

HuveGuard® HuveGuard®
Paracox® 8 x2 Paracox® 8 x2
Evalon Evalon
Livacox® Q Livacox® Q

Eimeria brunetti is missing

Eimeria mitis is missing

Too hot? E. praecox?

Composition of different EU coccidiosis vaccines Composition of different EU coccidiosis vaccines

E. acervulina E. maxima E. tenella E. mitis E. praecox E. necatrix E. brunetti E. acervulina E. maxima E. tenella E. mitis E. praecox E. necatrix E. brunetti

HuveGuard® HuveGuard®
Paracox® 8 x2 Paracox® 8 x2
Evalon Evalon
Livacox® Q Livacox® Q

8 different species: overload?

The only vaccine with
the 2 species for
longer living birds in a
Too (much?) attenuated different vaccine

Coccidiosis vaccination in longer

HuveGuard®
living birds
• Unique concept: 2 vaccines containing different
species

HuveGuard® MMAT HuveGuard® NB

Eimeria maxima
Eimeria mitis Eimeria necatrix
Eimeria acervulina Eimeria brunetti Pathogenic
Eimeria tenella
Pathology > 8 weeks of age

50 51

8
Huvepharma gut health training Oct 2018 Coccidiosis control - vaccines

Competition between species? Competition between species?

• Overlap in site of development

52 53

Coccidiosis vaccines Coccidiosis vaccines

Eimeria praecox Eimeria praecox

Eimeria acervulina Eimeria acervulina
Eimeria maxima Eimeria maxima
Eimeria mitis Eimeria mitis
Eimeria necatrix Eimeria necatrix
Eimeria tenella Eimeria tenella
Eimeria brunetti Eimeria brunetti

When vaccinating all species at the same moment, the young bird gets To aquire immunity cycling is needed, this requires multiplication of all the
into contact with many different antigens species present in the vaccine

55

Competition between species Split versus combined

It is known that competition might occur between
Eimeria species (Hein 1976; Mathis, 2005)

Is it better to split?

First immunity to broiler species- then to breeder

species

Each group 60 birds (3 replicates of 20 birds)

56 57

9
Huvepharma gut health training Oct 2018 Coccidiosis control - vaccines

Results – Trial split versus combined Results – Trial split versus combined
• Lesion scores 7 days post challenge • OPG acute phase

58 59

Conclusions –Split versus combined Coccidiosis vaccines

• Better protection for ‘split administerd’ Consequences of

vaccine and lower excretion of challenge attenuation
(wild) oocysts
• Especially towards E. necatrix, E. acervulina, asexual
replication
E. maxima
Less damage
• This could be attributed to less Lower reproduction potential
interference between different Eimeria
species (overload of antigens) Differences between vaccines!

60 61

Immunity IMMUNITY

1 2 3
Coccidiosis vaccines are live vaccines
Multiplication and cycling of the vaccine is
necessary

Correct application and cycling

are major keys to success!
Vaccination Cycling

10
Huvepharma gut health training Oct 2018 Coccidiosis control - vaccines

Vaccination in breeders
and layers

Protection in challenging
environments

64 65

Cycling pattern in breeders and layers Lesions in breeders and layers

Registration field trials Registration field trials

HuveGuard®

HIGH OPG

Other EU breeder vaccine

Low lesions 68

Cycling pattern in breeders and layers Follow up- Cycling

Registration field trials
Closed Aviaries- OPG- sampling 3/week
350,000
300,000
250,000
200,000
150,000
100,000
50,000
0
6 7 8 9 14 15 16 22 23 24 29 30 31 36 37 38 43 44 45 50 51 57 58 59 64 65 66 71 72 73 78 79 80 85 86 87 92 93 94 98 99 100105106107112113114119120121

E. acervulina E. tenella E. maxima E. brunetti E. necatrix/praecox E. mitis

Ground reared - OPG - sampling 3 days/week

350,000
300,000
250,000
200,000
150,000

HuveGuard® vaccination will result in high OPG and low lesions. 100,000

High OPG is beneficial for vaccine cycling which is necessary to build

50,000
0
6 7 8 14 15 16 20 21 22 23 27 28 29 42 43 44 48 49 50 56 57 58 63 64 65 70 71 72 77 78 79 84 85 86 91 92 93 98 99 100 104105106 111112 113119120 121

up solid immunity E. acervulina E. tenella E. maxima E. brunetti E. necatrix/praecox E. mitis

11
Huvepharma gut health training Oct 2018 Coccidiosis control - vaccines

Species when multiple samplings PCR

Species of average samples versus pool
7
6
5
4
3
2
1
0
Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 Week 7 Week 8 Week 9 Week Week Week Week Week Week Week Week
10 11 12 13 14 15 16 17

Species in 3 samples Species in Pool

Species of average samples versus pool

7
6
5
4
3
2
1
0
Woche 1 Woche 2 Woche 3 Woche 4 Woche 5 Woche 6 Woche 7 Woche 8 Woche 9 Woche Woche Woche Woche Woche Woche
10 11 12 13 14 15

Species Average Spezies Pool

Slide 71 72 Slide 72

Cycling for effective protection

OPG= 144.000 OPG= 50.000

100

90

80

70

60

50
OPG %
40 PCR-%
30

20

10

0
E. acervulina E. tenella E. maxima E. brunetti E. necatrix/praecox E. mitis

73

Immunity in field conditions Immunity in field conditions

• Comparison of coccidiosis treatments after Eu breeder HuveGuard® P-value
vaccination : vaccine MMAT and NB
• Results of rearing and production flocks Total Vacc Flocks 379 107
• From one breeder organization in Europe Treated >8 wks 27 1 0,016
• Same set of farms, same breeds, same housing % 7,1% 0,9%
conditions
• 2011-2016 Statistically significant (p<0,05) lower
number (>7 times less) of coccidiosis
• Only data from flocks with age >8 weeks, treatments needed when vaccinated with
when immunity is supposed to be HuveGuard® compared to other EU breeder
established
vaccine

12
Huvepharma gut health training Oct 2018 Coccidiosis control - vaccines

Immunity in field conditions Treatments rearing pullets

• Comparison of coccidiosis treatments Hatchery Hatchery

after vaccination : Paracox® 8 HuveGuard® MMAT and NB
• Results of rearing and production flocks
Period 2012-2017 Period 2015-2017
• From one rearing pullet organization in
Europe
• Same set of farms, same housing conditions Hatchery Hatchery
• 2012-2017 Hipracox ® Hipracox ® + HuveGuard® NB

Period 2015 Period 2015-2016

Treatments Cycling for effective protection

Total treatments after 5 weeks of age
Number Vaccine % of treatments % Tylosin % Toltrazuril
of flocks
39 Hipracox 15 10 8
39 Hipracox+NB 18 18 3
107 MMAT+NB 3 3 1
182 P8 17 17 3

Treatment in % after 5 weeks of age

Number Vaccine % of treatments % Tylosin % Toltrazuril
of flocks
107 MMAT+NB 3a 3 1
182 P8 17 b 17 3

p < 0,005

Coccidiosis vaccination in broilers

Vaccination in broilers

Anticoccidial
products

Restore your broiler house

Vaccines
81 82

13
Huvepharma gut health training Oct 2018 Coccidiosis control - vaccines

US Vaccine Usage over the Years US Vaccine Usage over the Years
35.0% 33%
% broiler cox vaccinated in US 31%
30.0% 70%
26% % of broiler vaccinated by month (US)
25.0% 23% 60%

50%
20.0%
17%
14% 14% EU: 3-4 % 40%
15.0% 13%
11.0% 30%

10.0%
20%

5.0% 10%

0.0% 0%

Dec-08

Dec-09

Dec-10

Dec-11

Dec-12

Dec-13

Dec-14

Dec-15

Dec-16

Dec-17
Sep-08

Mar-09

Sep-09

Mar-10

Sep-10

Mar-11

Sep-11

Mar-12

Sep-12

Mar-13

Sep-13

Mar-14

Sep-14

Mar-15

Sep-15

Mar-16

Sep-16

Mar-17

Sep-17

Mar-18
Jun-08

Jun-09

Jun-10

Jun-11

Jun-12

Jun-13

Jun-14

Jun-15

Jun-16

Jun-17

Jun-18
2009 2010 2011 2012 2013 2014 2015 2016 2017

83

Why all the Focus on ABF Chicken ABF is Going Mainstream

in US?
• Consumer activists are increasingly • Larger integrators • Smaller integrators
driving the conversation about food already producing have been ABF for
• Urban myth has become the new reality: ABF birds some time for niche
• Tyson, Pilgrims, GNP, markets
truth is rejected & perception is reality Fieldale Farms, • Hains, Bell & Evans,
• Producers are responding to consumer Perdue Joyce, Murrays,
pressure & the ability to market to a niche Millers
• Consumers believe Ab use in food
animals causes Ab resistance

85 86

Objective of using vaccines

Breeders Layers Organic Broilers
Short

Coccidiosis control in the vaccinated flocks

Restoration of
anticoccidial
Long

Uniformity sensitivity

88

14
Huvepharma gut health training Oct 2018 Coccidiosis control - vaccines

Composition of different EU coccidiosis vaccines

Long Term Objective
E. acervulina E. maxima E. tenella E. mitis E. praecox E. necatrix E. brunetti

Vaccination HuveGuard® MMAT

Paracox® 5 x2
Hipracox®
• Repopulation: replacement of drug resistant
Livacox® T
strains with vaccine sensitive strains
• Restoration of anticoccidial efficacy =>
performance!

Composition of different EU coccidiosis vaccines Composition of different EU coccidiosis vaccines

E. acervulina E. maxima E. tenella E. mitis E. praecox E. necatrix E. brunetti E. acervulina E. maxima E. tenella E. mitis E. praecox E. necatrix E. brunetti

HuveGuard® MMAT HuveGuard® MMAT

Paracox® 5 x2 Paracox® 5 x2
Hipracox® Hipracox®
Livacox® T Livacox® T

Only vaccine that contains

Eimeria mitis is missing Eimeria praecox

Not enough attenuated?

Composition of different EU coccidiosis vaccines Composition of different EU coccidiosis vaccines

E. acervulina E. maxima E. tenella E. mitis E. praecox E. necatrix E. brunetti E. acervulina E. maxima E. tenella E. mitis E. praecox E. necatrix E. brunetti

HuveGuard® MMAT HuveGuard® MMAT

Paracox® 5 x2 Paracox® 5 x2
Hipracox® Hipracox®
Livacox® T Livacox® T

Only vaccine that contains

two strains of Eimeria
maxima

Too attenuated?

15
Huvepharma gut health training Oct 2018 Coccidiosis control - vaccines

Broiler vaccines comparison

• Effect of the vaccines

B-Act®
Bacillus licheniformis
• Environment with no challenge
• Every bird is vaccinated individually

• Vaccines
• HuveGuard®MMAT ● HuveGuard®MMAT+B-Act®
• Hipracox®
• Paracox®5

96

Lichenicidin
• Bacillus licheniformis

Formation of lichenicidin

• Antimicrobial peptide
• Encoded on bacterial genes
• Active in nanomolar concentrations
• No resistance

• Inhibition of Clostridium perfringens

97 98

Lesion scoring : averages Lesionscoring- field studies

Registration field trials
HuveGuard® MMAT HuveGuard® MMAT and B-Act®
1.4 1.4
1.2
1.2 1.2 1.1
1.60
1 1
0.8 0.8
0.6 0.6 1.40
0.6 0.6
0.4
Average Total ILS

0.4 0.3 0.3 0.4

0.2 0.2 0.2 0.2 1.20
0.2 0.1 0.1 0.2
0 0 0 0 0
0 0 1.00
15 22 29 15 22 29

Eimeria acervulina Eimeria maxima Eimeria tenella Eimeria acervulina Eimeria maxima Eimeria tenella 0.80

0.60
Hipracox® Paracox® 5
1.4 1.4 0.40
1.2 1.1 1.2
1 1 0.20
0.8 0.8 0.7

0.6 0.5 0.6 0.5

0.00
0.4 0.4 0.4
0.4 0.3 0.3 0.3 0.4 day 7 day 14 day 21 day 28 day 35 day 38-42
0.1 0.1
Hipracox® Paracox® 5
0.2 0.2

HuveGuard®
0 0 0 0 0 0
0 0
15 22 29 15 22 29
101
Eimeria acervulina Eimeria maxima Eimeria tenella Eimeria acervulina Eimeria maxima Eimeria tenella

16
Huvepharma gut health training Oct 2018 Coccidiosis control - vaccines

Lesionscoring- field studies Lesionscoring- field studies

Registration field trials
Vaccine cycling Field cycling
HuveGuard® : Lesions
1.60 1.60

1.40
at an early age 1.40
Average Total ILS

Average Total ILS

1.20 1.20

1.00 1.00

0.80 0.80

0.60 0.60

0.40 0.40

0.20 0.20

0.00 0.00
day 7 day 14 day 21 day 28 day 35 day 38-42 day 7 day 14 day 21 day 28 day 35 day 38-42

HuveGuard® Hipracox® Paracox® 5 HuveGuard® Hipracox® Paracox® 5

102 103

OPG- field studies OPG- field studies

Registration field trials

140000 140000

Fast
120000 120000

100000 100000

80000 80000
OPG

OPG

60000

40000
60000

40000
HIGH LOW
20000 20000

0 0
day 7 day 14 day 21 day 28 day 35 day 38-42 day 7 day 14 day 21 day 28 day 35 day 38-42

HuveGuard® Hipracox® Paracox® 5

Vaccine cycling Field cycling
104 105

Growth curve- OPG excretion Vaccination: protection

Challenge studies

• 3 vaccinated groups:
▪ HuveGuard® MMAT
▪ Hipracox® (vaccine 1)
▪ Paracox® 5 (vaccine 2)

• 2 control groups:
▪ uninfected, unvaccinated control (UUC)
▪ infected, unvaccinated control (IUC)

106
107

17
Huvepharma gut health training Oct 2018 Coccidiosis control - vaccines

Vaccination: protection Vaccination: protection

Challenge studies

• Vaccination of the birds by coarse spray on

feed at 1 day of age (except for IUC and UUC)

• At the age of 20 days all groups, except for

the UUC group, were infected by gavage with
an inoculum containing E.acervulina, E. Hipracox Paracox5

maxima, E. mitis and E. tenella (European

Highest body
origin) weight and DWG
Hipracox Paracox5

108 109

Vaccination: protection Vaccination for broilers

• Increasing attention :
• Customer/retailer demand
Lowest • Increasing resistance to anticoccidial products
FCR (additional rotation tool)
• Mass application (hatchery)
• Fast and efficient cycling is needed to
obtain a quick and solid immunity
Hipracox® Paracox® 5
• Performance results are acceptable!

110

Coccidiosis vaccination =
Performance after vaccination
expensive?
AVERAGE DAILY GAIN
72
Vaccines Price/1000 price/bird
70 before vaccination ADVENT € 6.00 1,000 € 0.0060
68 HuveGuard®MMAT € 24.00 1,000 € 0.0240
66
64
HuveGuard®MMAT+ B-Act® € 0.0245
62 during vaccination Coccidiostat price/bird
60
Full Sacox € 12.44 1,000 € 0.0124
58
1 2 3 4 Max/Mont/blanco € 19.67 1,000 € 0.0197
House
ANTIBIOTIC USE Max/Mont/Mont € 28.61 1,000 € 0.0286
90 Full Maxiban € 41.47 1,000 € 0.0415
ANIMAL DAY DOSE/ANIMAL YEAR

80
70
60
Maxiban : € 14
50
Full: 0-42 days
40 BEFORE Monteban : € 6.5
30 Shuttles: 0-25/25-32/32-42
20
DURING
Sacox: € 4.5
10
0
1 2 3 4
House

112

18
Huvepharma gut health training Oct 2018 Coccidiosis control - vaccines

Vaccination General Conclusions

• Importance will increase in the future • Damage caused by coccidiosis is huge

▪ Direct Damage
▪ disease (diarrhoea)
• Tailor made solutions! ▪ mortality
▪ decreased performance
▪ Indirect Damage
• More modern for competing in challenging ▪ Dysbacteriosis, bacterial enteritis, Necrotic enteritis
environment (breeders, layers, broilers) ▪ Wet litter with accompanying issues (breast blisters, hock
burns, decreased performance, downgrading & rejections
in slaughterhouse)
▪ Increased susceptibility to infection with other (zoonotic)
agents

115

General Conclusions Thank you for your attention !

• This damage must be minimized by

appropriate use of anticoccidial
products and programs

• Vaccines are a valuable tool for

protection in longer living birds and Questions ???
restoration of sensitivity

116 117

19