This document summarizes a study comparing neutralizing antibody response to heterologous protection from foot-and-mouth disease virus (FMDV). The study found that neutralizing antibody titers were a poor predictor of heterologous protection compared to homologous protection. Vaccination with SAT2/SAU/2000 generated low potency ratios against heterologous challenge strains SAT2/BOT/18/09 and SAT2/LIB/40/2012 compared to the r1-value, indicating other immune mechanisms beyond neutralizing antibodies provide heterologous protection against FMDV.

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A. Dekker and C. Baars
Wageningen Bioveterinary Research / Lelystad / the Netherlands.
Neutralising antibody response poor
predictor of heterologous protection

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Background
● The (neutralising) antibody response is a good predictor
of homologous protection
● No in vitro correlates of heterologous protection are
available
● Is the r1-value a good predictor of potency ratio?
𝑃𝑜𝑡𝑒𝑛𝑐𝑦 𝑟𝑎𝑡𝑖𝑜 =
𝐻𝑒𝑡𝑒𝑟𝑜𝑙𝑜𝑔𝑜𝑢𝑠 𝑝𝑜𝑡𝑒𝑛𝑐𝑦
𝐻𝑜𝑚𝑜𝑙𝑜𝑔𝑜𝑢𝑠 𝑝𝑜𝑡𝑒𝑛𝑐𝑦

3. 3
21 day post vaccination sera from SAT2/SAU/2000
● Estimate the
homologous
potency
● Calculate
potency ratio
● Compare with
r1-value
Challenge strain Potency 95% CI
SAT2/SAU/2000 >32 NA
SAT2/SAU/2000 24 <14,42>
SAT2/SAU/2000 42 <16,108>
SAT2/BOT/18/09 1.5 <0.6,4>
SAT2/LIB/40/2012 11 <4,25>

4. 4
Calculate titre that predicts 50% protection
● Red line logistic
regression curve using
the observations
● Blue line logistic
regression curve using
slope of other studies
● Heterologous studies
significant different slope
0.0 0.5 1.0 1.5 2.0 2.5 3.0
0.00.20.40.60.81.0
VNT titre (log 10)
Fractionprotected

5. 5
Comparison of potency ratio and r1-value
● Estimation of homologous potency based on relation
antibody response and dose
Challenge strain r1-value 95% CI
potency
ratio
SAT2/BOT/18/09 0.05 <0.04,0.06> 0.01
SAT2/LIB/40/2012 0.1 <0.09,0.12> 0.04

6. 6
Conclusion
● Potency ratio in both experiments lower than r1-value
● Different slope (less steep) in heterologous protection
test of the logistic regression curve, indicative of other
immune mechanisms than neutralisation
● Further studies using LPB ELISA

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