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EVALUATION OF THE IMMUNE RESPONSE
3.4 Evaluation of immune responses in vaccinated animals under field conditions This field study method is proposed for use once a vaccine has been selected in order to gain a better understanding of how it will behave in a larger group of animals than that utilised in the pre-purchase trial described in section 3.3 above. If there is no requirement to undertake the pre-purchase trial, then some of the objectives of that trial (such as serological test calibration) can also be accomplished after vaccine purchase using this field study. The approach is one of a longitudinal study, in which a selected cohort of animals is vaccinated and monitored over time. A suggested protocol is provided in this section (with the statistical background explained in more detail in Annex 2). The specific objectives for such an evaluation are as follows: – to provide an accurate estimate of the proportion of animals that will develop an SP antibody titre equal to or greater than a pre-specified level at day 28 after vaccination; – to provide an accurate estimate of the proportion of animals that will maintain an SP antibody titre equal to or greater than a pre-specified level at days 56 and 168 (after first vaccination); – to provide an accurate estimate of the range and mean antibody response at days 28, 56 and 168 (after first vaccination); – to indicate whether or not the vaccine elicits NSP antibody responses in vaccinated animals. Depending on the data available, these studies may be used to evaluate protection as follows: – In cases in which countries have no data on correlation between serology and protection, results from these trials (the mean, the distribution and the 95% confidence intervals [95% CIs] of titres) may help to establish provisional cut-off values to be used in wider sero-surveys. – In cases in which countries have enough data to establish a provisional cut-off value (e.g. ‘highly protected’ and ‘poorly protected’), the main expected result would be the proportion of animals in each of those two groups. In addition to the mean, the
distribution and the 95% CI of titres will help to refine the cut-off values. – In the case in which a country has established the relationship between titres and protection, the results will allow estimation of the expected level of protection of animals belonging to the vaccinated population under field conditions. Any assessment of immune responses to vaccination requires a source of FMD seronegative animals and a holding facility or farms where the animals can be maintained and monitored under conditions that minimise the risk of the animals becoming infected with FMDV. In countries with a high incidence of FMD (PCP-FMD stage 1 or 2 ) and/or where vaccination has been widely used, it may be difficult to find animals free of antibodies to the virus resulting from either active or passive (colostral) immunisation. In such situations, in order to ensure a low likelihood of exposure to FMD while the monitoring is on-going, the epidemiological units (epi-units) could be selected based on knowledge of no past exposure to FMDV in the previous two years. The following protocol may be used to evaluate the immune response in vaccinated animals under field conditions: a) suggested values for expected proportion of animals that will develop a specific level of antibodies in the age category 6–12 months – 85%; b) allowable standard error – 10%; c) level of confidence – 95%. – Based on the above values, 49 animals are need for the study. – Increase the sample size to 55 animals, in order to compensate for possible withdrawals, previous exposure to the virus or problems with sample analysis. – Animals from 6 to 12 months of age, known to be free of FMD antibodies (NSP and SP to vaccine strains) should be selected by either simple random sampling or systematic random sampling. – Select a sufficient number of epi-units to carry out the trial to achieve the required number of animals. Ideally the epi-units selected should have little chance of being exposed to field viruses (no FMD detected in the past two years) in order not to confound the effect of the vaccine with the effect due to exposure to field virus. – Animals should be individually identified. – Collect blood samples at days 0 (time of first vaccination), 28 (time of booster dose), 56 and 168. Foot and mouth disease vaccination and post-vaccination monitoring. Guidelines
