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Vaccination: overcoming the
constraints to achieving effective
immunity rates
A. Dekker
Vaccine does not work
To many animals without sufficient immunity
No vaccination
Poor vaccine (quality control in session 2D)
Short duration of immunity
No vaccine response due to maternally derived Ab's
Poor vaccine match (session 2B)
Insufficient data
No control with vaccine alone
Number of FMD cases in the Netherlands
100000
Start mass vaccination cattle
10000
End vaccination campaign
1000
100
10
1
2004
1999
1994
1989
1984
1979
Year
1974
1969
1964
1959
1954
1949
1944
1939
1934
1929
1924
1919
1914
1909
1961 – 1967
outbreaks in
non-vaccinated
pigs due to
introduction from
neighbouring
countries
Control
successful after
European coordination of
control
Number of cases
In field studies often short lived Ab response
Woolhouse, M. E. J.,
Haydon, D. T., Pearson, A.
& Kitching, R. P., 1996,
Failure of vaccination to
prevent outbreaks of footand-mouth disease,
Epidemiology and Infection
116(3):363-371.
Frenkel vaccine could induce long lasting
immunity after repeated (3) vaccination
Terpstra, C., van Maanen,
C. & van Bekkum, J. G.,
1990, Endurance of
immunity against foot-andmouth disease in cattle
after three consecutive
annual vaccinations,
Research in Veterinary
Science 49(2):236-242.
Good duration of immunity in experiments
2.5
titre (10log)
2
1.5
Cattle
Pig
1
Sheep
0.5
0
0
20
40
60
80
100
120
140
Days after vaccination
Type O Cedivac vaccine
DOI studies in 1991 and
2007
160
180
200
Comparison of titres found in field and experiments
for vaccine release (Netherlands 2001)
• In the field 24% ≤ 1.05
1000
• median titre ≈ 1.50 similar in
both populations
5000
4000
3000
2000
1000
VNT titre
>2.55
2.55
2.4
2.25
2.1
1.95
0
1.8
• Experimental sera from pigs
6000
1.65
• In the field only cattle was
sampled
• Agreement between both
results
1.5
VNT titre
>2.85
2.85
2.55
2.25
1.95
1.65
1.35
1.05
<1.05
<1.2
<0.9
<0.6
0
1.35
200
1.2
400
1.05
600
0.9
800
Weighed used vaccine
Number of sera
1200
What is the difference between various studies?
Vaccine quality
Amount of antigen
Quality of the antigen (146S vs 12S)
Quality of the adjuvant
Dutch 2001 results show experiments can be a
predictor for the result in the field
Vaccine trial when buying vaccine
Vaccinate at least 5 cattle
Collect serum samples (sufficient amounts)
0, 1, 2, 3, 4, 6 and 8 weeks after vaccination
Repeat test at least at half the shelf life
Use sera as standards when repeating tests
Antibody concentration not always correlated with
protection
Interference of maternally derived Ab's
10log
VNT titre
2.0
1.5
1.0
0.5
1
2
3
4
5
6
Weeks post vaccination
Barteling, S. J., Van Maanen, C., Yadin, H. & Anemaet, D. A. J., 1990, A footand-mouth disease vaccine bank: purified inactivated antigen stored at ultra-low
temperatures for the rapid preparation of double oil emulsion (D.O.E.) vaccines,
in: European commission for the control of FMD, session of the research group
of the standing technical committee, Lindholm. Denmark.
Immune response in presence high Ab titre
Spath, E. J. A., Smitsaart, E., Casaro, A. P. E., Fondevila, N.,
Fernandez, F., Leunda, M. R., Compaired, D., Buffarini, M. & Pessi, H.,
1995, Immune response of calves to foot-and-mouth disease virus
vaccine emulsified with oil adjuvant. Strategies of vaccination, Vaccine
13(10)::909-914.
2.4
2.4
2.1
2.1
1.8
1.8
A Turkey 14/98 VNT titre
A22 Iraq VNT titre
Recent studies in calves (see poster)
1.5
1.2
0.9
1.5
1.2
0.9
0.6
0.6
0.3
0.3
0.0
0.0
0
2
4
Weeks post-vaccination
6
0
2
4
Weeks post-vaccination
6
Recent studies in pigs (see poster Chenard et al.)
2.00
1.80
Mean VNT titre
1.73 in piglets
after colostrum
uptake
1.60
VNT titre 1.50 in adult
pigs 4 weeks postvaccination with
a 6 PD50 vaccine
A Turkey Log 10 VNT Titre
1.40
1.20
1.00
Piglets vaccinated at
age of:
0.80
2 weeks
4 weeks
6 weeks
8 weeks
not vaccinated
2 weeks no MDA
0.60
0.40
0.20
0.00
-12
-10
-8
-6
-4
-2
0
Weeks post vaccination
2
4
6
8
Conclusion
In emergency vaccinate also young animals
Study best time for vaccination in young animals
every time vaccine is changed
Higher Ab's in dams might prevent response if offspring
Better adjuvant might induce Ab response earlier
Insufficient data from field studies with good
quality vaccine (with quantified quality)
Epidemiological needs for vaccine
1972 OIE sets standard of 70% protection
If R0 is 3.3 then with 30% susceptibles Rv ≈ 1
• Fraction to be removed 1 – 1/R0
Within herd R0 is higher (6 in cattle 40 in pigs)
Between herd transmission in UK R0=3.6 (Ferrari, M. J., Bjørnstad,
O. N. & Dobson, A. P., 2005, Estimation and inference of R0 of an infectious pathogen by a removal method,
Mathematical Biosciences 198(1):14-26.)
Current vaccines (3 PD50/dose, 70% protection)
work only with concurrent movement control
Experimental "within pen" transmission
studies in the Netherlands
Pigs
Calves
O Manisa vaccination – O Netherlands 2001 challenge
Dairy cattle
O Taiwan vaccination – O Taiwan challenge
O Manisa vaccination – O Taiwan challenge
O Manisa vaccination – O Netherlands 2001 challenge
O Manisa vaccination – O Netherlands 2001 challenge
Sheep
O Manisa vaccination – O Netherlands 2001 challenge
Asia- Shamir vaccination – Asia-1 Turkey challenge
Experimental design
Non-vaccinated and
vaccinated groups
Half the animals infected
other half exposed by
contact
Calculate
Average number of new
infections per infectious
individual (R)
Average number of new
infections per day
Infectious period
Pig experiments with O Taiwan challenge
Vaccination O Manisa or O Taiwan 14 days
before infection
No infection of inoculated pigs (intradermal in the bulb
of the hoof)
Rv cannot be estimated (no infectious pigs)
Vaccination O Taiwan 7 days before infection
No vaccine
Single dose
4-fold dose
ß
6.1
2.0
0.4
T
6.5
5.3
2.3
Rv
40
11
1
ß = number of new infections per infectious individual per day
Pig experiments with O Netherlands
challenge
Vaccination O Manisa 14 days before infection
Infection by direct contact to non-vaccinated inoculated
pigs
ß
T
Rv
No vaccine
6.8
6.6
44
Single dose
0.7
4.7
3.3
ß = number of new infections per infectious individual per day
Reproduction ratio R in calves, dairy cattle
and sheep (O manisa vaccine and O NET challenge)
Non-vaccinated
Calves
Dairy cattle
Sheep
2.5
∞
1.14
Vaccinated 2 weeks before challenge
Calves
0.2
Dairy cattle
0
Sheep
0.2
Conclusion
Emergency vaccination with potent vaccines is a
very good tool to control FMD outbreaks
Vaccination significantly reduces "within pen"
transmission
Most data obtained 2 weeks after vaccination
R<1 only small outbreaks
Good quality vaccines should be sufficient for
eradication in endemic areas
Based on published data from field trials there is
still much room for improvement