THE SEROLOGICAL RESPONSE INDUCED BY INACTIVATED FMD VACCINE IN ISRAEL – CLINICAL TRIALS IN A DAIRY FARM Ehud Elnekave, Aldo Dekker, Phaedra Eble, Froukje van Hemert-Kluitenberg, Boris Gelman, Nick Storm, Eyal Klement

Before we start… This Presentation is based on the fruits of a PhD performed by Dr. Ehud Elnekave Israeli Kimron Veterinary institute Boris Gelman Nick Storm CVI, The Netherlands Aldo Dekker Phaedra Eble Froukje van Hemert-Kluitenberg

FMD vaccination in Israel Commercial vaccine - Merial® High potency dose (PD50≥6) Same vaccine is used for routine and emergency vaccination Cattle – Trivalent vaccine (O, A and ASIA-1) 1st vaccination between 2-3 months of age 2nd vaccination up to 3 months later Annual vaccination

Vaccine effectiveness in Cattle – prior experience from Israel Dairy cattle are rarely affected during FMD outbreaks When they are affected only young animals show clinical disease Young animals are (up to two years old) are only partially protected from clinical morbidity despite multiple vaccinations (Elnekave et al. 2013) Emergency vaccination is highly effective in prevention of clinical and subclinical morbidity (Elnekave et al. 2013) Elnekave E, Li Y, Zamir L, Even-Tov B, Hamblin P, Gelman B, Hammond J, Klement E. (2013) The field effectiveness of routine and emergency vaccination with an inactivated vaccine against foot and mouth disease. Vaccine. 31:879-85

Hypothesis and Questions It takes more than a certain number of vaccinations to elicit a stable immune response Age of initial vaccination influences not only the immune response at the initial phase but also at the later stages What is the number of vaccinations needed to elicit a stable immune response? What is the ideal age for administration of first vaccination and what is the best vaccination schedule to elicit a good immunological coverage during the first two years of life?

Research aims Estimation of the long term antibody dynamics: Routinely vaccinated cows and heifers of different vaccination statuses Non vaccinated calves – After ingestion of colostrum After vaccination in different ages and different levels of maternal immunity

Antibody dynamics in response to vaccination Study design Vaccination trial # of animals 54 45 Cows Heifers Trivalent – day 0 ≥6 vac. 5 vac. 4 vac. 3 vac. 2 vac. 1 vac. Trivalent 1 2 4 6 8 12 16 24 36 51 55 77 102 weeks Trivalent

Antibody dynamics in response to vaccination Vaccine serotype O-4625 Groups vaccinated less than 3 times: Rapid increase in the antibody titers after vaccination Followed by quite rapid decrease Groups vaccinated 4 times or more: No reaction to vaccine administration Consistent antibody levels

Average neutralizing antibody titer before vaccination in the 1st (a) and the 2nd (b) years

Proportion of animals with titers higher than cut of log10=2 during the 1st year

The long term effect of age and maternally derived antibodies on the serological response in young dairy calves

Maternal Antibody Decay Half-life=22 days

Antibody dynamics in response to vaccination

Average neutralizing antibody titers (NAT) above cut-off titer of 2 Average neutralizing antibody titers (NAT) above cut-off titer of 2.0 between the age of six months and 1.5 years

Percentage of time over any cutoff

Conclusions Five vaccine doses provide long lasting immunity Given the fact that emergency vaccination is always warranted during an outbreak, the effectiveness of vaccinating after 5 vaccinations should be re-assessed Vaccination of calves prior to the age of three months does not elicit good AB response not just after vaccination but also impairs the entire immunological response later on.

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