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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