Vaccinating goats with live wildtype Mccp strain
ILRI181 induces protective immunity against
CCPP
Elise Schieck
European Mycoplasma Conference, London, 18-19 March 2019

Background
Is the challenge model too harsh?
Is there a future for Mccp live vaccines?
Test the challenge model against the saponized bacterine vaccine
Test whether the wild type ILRI181 can induce a protective immune
response after subcutaneous immunisation

Trial design
Entry
ABSL2
Vaccination Challenge End of Trial,
Necropsies
Days post
vaccination
-14 0 29 50

Trial design
Vaccinations, subcutaneous:
T1 (live wild-type ILRI181)
T2 (inactivated ILRI181)
T3 (inactivated Abomsa (CIRAD))
T4 (control, PBS)
• Body temperature >40.5 C for >3days
• Body weight loss >10% in 7 days
• Breathing frequency >50/min for >3days
• Signs of moderate to severe pain
Eight goats per group, randomised, blinded:
Monitoring and sampling:
Daily: Rectal temperature, heart
rate, breathing rate.
Three times weekly: weight.
Sampling, serum: twice weekly
End-point criteria:

Challenge with live wild-type Mccp ILRI181
Liljander et al. 2019
0 1 4
Intranasal
108 CCU
Transtracheal
108 CCU
Days post challenge
29 30 33 Days post vaccination

Results - survival
Log-rank test:
T1 vs T4: p=0.0001
T2 vs T4: p=0.0001
T3 vs T4: p=0.0014
T1: Live ILRI181
T2: Inactivated ILRI181
T3: Inactivated Abomsa
T4: PBS
0 5 10 15 20 25 30 35 40 45 50 55
0
50
100
Days post vaccination
Percentsurvival
ChallengeVaccination

Results – Clinical monitoring
T1: Live ILRI181
T2: Inactivated ILRI181
T3: Inactivated Abomsa
T4: PBS
-15 -10 -5 0 5 10 15 20 25 30 35 40 45 50
38
39
40
41
42
Days post vaccination
Temperature(°C)
ChallengeVaccination

Results – Clinical monitoring
-15 -10 -5 0 5 10 15 20 25 30 35 40 45 50
38
39
40
41
42
Days post vaccination
Temperature(°C)
ChallengeVaccination
-15 -10 -5 0 5 10 15 20 25 30 35 40 45 50
10
20
30
40
50
60
Days post vaccination
Breathingrate(perminute)
ChallengeVaccination
-15 -10 -5 0 5 10 15 20 25 30 35 40 45 50
60
70
80
90
100
110
120
130
140
Days post vaccination
Heartrate(beatsperminute)
T1: Live ILRI181
T2: Inactivated ILRI181
T3: Inactivated Abomsa
T4: PBS
ChallengeVaccination
-15 -10 -5 0 5 10 15 20 25 30 35 40 45 50
25
30
35
40
45
Days post vaccination
bodyweight(kg)
ChallengeVaccination
A B
C D
A: Body temperature
B: Heart rate
C: Breathing frequency
D: Body weight

Results – Necropsy
Schematic subdivision of lungs into triangle
sections for pneumonia and pleuritis scoring
purposes

Results – Pathology results
Group Vaccine Animal ID
Day of
euthanasia
(days post
challenge)
Pneumonia
Pleural
fluid
collected
(ml)
Lung
consolidation
score
Pleuritis score
Fever
≥40,5 °C
Fever
<40,5°C
Coughing
several times
after
challenge
T1 Live ILRI181
CM259 15 yes 320 16,9 16,9 yes yes yes
CP006 21 no 0 0 0 no no no
CP012 21 no 0 0 0 no yes yes
CP015 22 no 0 0 0 no no no
CP017 22 no 0 0 0 no no no
CP018 22 no 0 0 0 no no no
CP029 23 no 0 0 0 no no no
CP030 23 no 0 0 0 no no no
T2
Inactivated
ILRI181
CM262 21 no 0 0 0,7 no no yes
CP008 21 no 0 0 0 no no no
CP016 21 no 0 0 0 no no yes
CP026 21 no 0 0 5,9 no no yes
CP001 22 no 0 0 0 no no no
CP020 22 no 0 0 0 no no no
CP022 22 no 0 0 0 no no yes
T3
Inactivated
Abomsa
(CIRAD)
CP005 13 yes 75 18,6 18,6 yes yes yes
CP004 14 yes 115 16,2 14,8 yes yes yes
CP028 15 yes 22 7,1 7,1 yes no yes
CP002 21 no 0 0 0 no yes no
CP013 22 no 0 0 1,5 no no no
CP021 22 no 0 0 0 no no no
CP023 23 no 0 0 0 no no no
CP025 23 no 0 0 0 no no no
T4 PBS
CP009 11 yes 70 16,3 16,3 yes no yes
CP003 12 yes 135 16,6 16,6 yes no yes
CP011 12 yes 45 15 14,3 yes no yes
CP014 12 yes 135 13,1 12,1 yes yes yes
CP019 13 yes 20 15,5 15,5 yes no yes
CP024 13 yes 150 20,1 20,1 yes yes yes
CP027 13 yes 295 17,1 17,1 yes yes yes
CP007 15 yes 75 16,2 15,5 yes yes yes
†
†
†

Results - Protection
Vaccination
group
Proportion
(euthanized/total)
Proportion
(euthanized/total)
In control group T4
χ 2 test Vaccine Efficacy
=Protection
against severe
disease/mortality
T1
(live
ILRI181)
1/8 8/8 p<0.001 87.5%
T2
(inactivated
ILRI181)
0/7 8/8 p<0.001 100%
T3
(inactivated
Abomsa)
3/8 8/8 p=0.009 62.5%

Results - Protection
Vaccination
group
Proportion
(clinical signs/total)
Proportion
(clinical signs/total)
in control group T4
χ 2 test Vaccine
Efficacy
=Protection
against clinical
signs: fever or
lesions
T1
(live ILRI181)
2/8 8/8 p=0.003 75%
T2
(inactivated
ILRI181)
2/7 8/8 p=0.005 71.4%
T3
(inactivated
Abomsa)
5/8 8/8 p=0.063 62.5%

Conclusion
Is the challenge model too harsh?
Is there a future for Mccp live vaccines?

Conclusion
Is the challenge model too harsh?
-Test the challenge model against the saponized bacterine vaccine
-No it’s not!
The challenge model will be very useful for testing novel vaccines
Is there a future for Mccp live vaccines?
-Test whether the wild type ILRI181 can induce a protective immune
response after subcutaneous immunization
-Yes there is!
The next challenge will be to get the right level of attenuation

Thank you!
Flavio Patrice Odhiambo Lameck Giuseppe Gesharisha Marren
Joerg Jores and Anne Liljander
Francois Thiaucourt and Lucia Manso-Silvan
Vish Nene and Jeremy Salt
Cecilia

This presentation is licensed for use under the Creative Commons Attribution 4.0 International Licence.
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