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TRANSCRIPT
FIELD TRIAL TO ESTIMATE THE EFFECTIVENESS OF THE VACCINATION PROGRAM IMPLEMENTED IN
THE MAGHREB REGION
E. Brocchi, N. Abouchoaib, F. El Mellouli, M. Bugnetti, F. Rosso, A. Ripani, G. Pezzoni, S. Grazioli
Global Vaccine Security - OS18: Oct 2018, Italy
OS18
Global Vaccine Security - OS18: Oct 2018, Italy E. Brocchi
Why in Maghreb countries?
Sequential incursions of exotic FMD viruses in North Africa
Vaccination is one of the most important tools to control FMD, either as routineor emergency vaccination
O/ME-SA/Ind2001from virus pool 2
A/Africa G-IVfrom virus pool 5
O/EA3from virus pool 5
2013-2015 2017 2018
Global Vaccine Security - OS18: Oct 2018, Italy E. Brocchi
Context and Objectives
Knowledge on vaccine effectiveness is strategic to predictwhether vaccination can contribute to FMD control
Confined field studies may provide preliminary estimates ofvaccine effectiveness
EuFMD, OIE Tunis, and IZSLER have jointly proposed a fieldvaccine trial to Algeria, Morocco and Tunisia to evaluate theeffectiveness of FMD vaccines currently used in each country
Here we report the results obtained from the trial conductedin Morocco
Global Vaccine Security - OS18: Oct 2018, Italy E. Brocchi
Experimental design
VACCINATION
GROUP 1. n. 20 cattle (6-8 month-old) – non vaccinated (NAIVE)
GROUP 2. n. 20 cattle (1-2 year-old) – previously vaccinated – last vaccination 3 months prior
SAMPLING SCHEME
Day 0: before vaccination
5 DPV - 10 DPV (vaccinated and naïve respectively): evaluation of early immune-response to vaccine
30 DPV: pick of humoral response
TESTING SCHEME
NSP-ELISA to prove absence of FMD virus circulation (ALL SAMPLES WERE CONFIRMED NEGATIVE) SP-ELISAs for antibodies to type O and type A (IZSLER kits) Virus Neutralization Tests (VNT) against:
the vaccine strains (homologous Ab) the field viruses (heterologous Ab)
neutralizing antibodies provide more accurate estimates of protection
VACCINE adopted in Morocco
Type O: O Manisa/O 3039 – 3 PD50
Type A: A/Eritrea 98 – 6 PD50
Global Vaccine Security - OS18: Oct 2018, Italy E. Brocchi
ELISA (IZSLER kits)
10 0
10 1
10 2
10 3
10 4
DD EE FF D E F
PRE-VACCINATEDNAIVE
Type A Ab
0 5 300 10 30
Threshold +/-
10 0
10 1
10 2
10 3
10 4
AA BB CC A B C
NAIVE PRE-VACCINATED
Type O Ab
DPV 0 10 30 0 5 30
(Lo
g 10)
Ab
tit
re
Threshold +/-
In previously vaccinated cattle, the booster vaccination elicited a strong and fast(5 DPV) increase of antibodies against FMDV serotype O
In the primary-vaccinated group only few animals showed sero-conversion toFMDV serotype O
Similar observations for FMDV serotype A, though more naïve calves showed seroconversion
Global Vaccine Security - OS18: Oct 2018, Italy E. Brocchi
-20
0
20
40
60
80
100
aa bb cc dd ee ff
ELISA (IZSLER kits)
TYPE O Ab TYPE A Ab
DPV 0 10 30
Perc
enta
gein
hib
itio
n–
scre
enin
g d
iluti
on
0 10 30
Threshold +/-
Seroconversion in NAIVE CATTLE
Though several NAÏVE calves did not achieve the standard threshold for positivity,there is of Ab production elicited by vaccination: percentage inhibition valuesincreased approaching the threshold.
Global Vaccine Security - OS18: Oct 2018, Italy E. Brocchi
VNT tests – type O antibodies
10 1
10 2
10 3
10 4
10 5
O P Q R S T U V Z
O ManisaVaccine strain
O Ind/2001Field strain
O PanasiaField strain
Previously VACCINATED
(Lo
g 10)
VN
T ti
tre
DPV 0 5 30 0 5 30 0 5 30
Booster vaccination induced comparable levelsof neutralising (protecting) antibodies againstthe vaccine and the field strains (homologousand heterologous immune response)
Cross-protective immunity 5 DPV
Seroconversion in all naïve animals
But lower Ab titres (with several calves not reaching a presumed protection threshold)
Similar kinetic and level of Ab against vaccine and field strains (cross-neutralization)
10 1
10 2
10 3
10 4
10 5
OO PP QQ RR SS TT UU VV ZZ
O ManisaVaccine strain
O Ind/2001Field strain
O PanasiaField strain
NAIVE – single vaccination
0 10 30 0 10 30 0 10 30
Global Vaccine Security - OS18: Oct 2018, Italy E. Brocchi
VNT tests – type A antibodies
10 1
10 2
10 3
10 4
10 5
G H I L M N
Vaccine strain(A/Eritrea 98)
Field strain(A/ALG 17)
Previously VACCINATED
(Lo
g 10)
VN
T ti
tre
DPV 0 5 30 0 5 30
Booster vaccination induced higher neutralisingtitres (≥5-fold) vs the type A vaccine strain(homologous Ab), but with a considerable levelof cross-reactivity vs the field strain
Confirmed fast immunity - 5 DPV - against bothviruses
10 1
10 2
10 3
10 4
10 5
GG HH II LL MM NN
Vaccine strain(A/Eritrea 98)
Field strain(A/ALG 17)
NAIVE – single vaccination
0 10 30 0 10 30
Seroconversion in all naïve animals
But significantly lower Ab titres
Partial cross-reactivity (with several calves not reaching a protective immunity against the field virus)
Global Vaccine Security - OS18: Oct 2018, Italy E. Brocchi
Conclusions
SP-ELISA provided results consistent with VNT forboost-vaccinated animals, whilst it was less sensitivefor detection of Ab in primary-vaccinated calves.
A booster vaccination is necessary to elicit a strongand fast rise of Ab, cross-neutralizing field circulatingviruses, despite limited antigenic matching betweenstrains.
Simple and feasible field vaccine trials enableproducing relevant information, contributing tooptimizing FMD control and preparedness againstreoccurrence of outbreaks.
THANKS FOR THE ATTENTION
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