EVALUATION OF THE IMMUNE RESPONSE Chapter 3 (23-37)
3.1 Introduction Estimating the immunity of the population targeted for protection by vaccination is the core of PVM, as it is a key indicator of how well vaccination has been carried out and whether or not protection against infection is likely. However, interpretation of wider field studies of population immunity requires an understanding of the serological responses that can be expected from the vaccine that is used, as well as how these relate to protection from disease and virus transmission. Evaluation of the immune response to vaccination is also an important method for vaccine selection. Therefore, this chapter describes the principles of selection and interpretation of PVM serology, as well as protocols for evaluating post-vaccination immunity before and after vaccine purchase and widespread use. A summary of the issues addressed and the approaches recommended for evaluating immunity is provided in Table II. FMD vaccines elicit an antibody response against the structural proteins (SP) of the virus that make up the virus shell or capsid, and therefore serological tests can be used to identify vaccinated animals in a naïve population. There is also a correlation between the levels of these antibodies and the protection induced by the vaccine, and it is possible to establish the threshold of antibodies that equates to a given level of protection in the individual animal (36). However, this threshold varies between vaccines and serological tests and according to the time after vaccination (40). It can be established, for a particular vaccine and serological test, by comparing the vaccine-induced serological responses with the vaccine-induced protection in animals challenged with live virus in a potency test (3, 37). This provides a rational threshold for evaluating protection in a population, even if the strength of the challenge may differ under field conditions from that of a potency test. In the absence of a known correlation between protection and antibody titre, the serologically determined response to vaccination can still be used to inform vaccine selection and monitor the vaccination programme. For example, a crude assessment of quality can be made to ensure that the vaccine in question is able to induce an antibody response, while the relative potency of alternative vaccine supplies can be compared in terms of the comparative levels of antibodies
they induce. The sera obtained from such trials can also be used to calibrate the testing of the wider vaccinated population, for example to monitor for any diminution in antibody levels that might result from variability in vaccine batches or an inadequate cold chain. Similarly, when monitoring population immunity, even if the correlation between serology and protection is uncertain, serology can be used to compare differences in immunity between subpopulations, for example according to animal age, or to compare regional effectiveness in vaccine delivery. In practice, for FMD, defining a protective titre of antibodies is quite difficult, as this will be affected by many variables (the type of vaccine, the type and reproducibility of the test used to measure the serological response, the strain of virus against which protection is needed, the weight of challenge, etc.). Three possible approaches can be considered: 1. Where the protective titre for a particular vaccine, challenge virus and test has been defined, allowing vaccinated animals to be tested and categorised as protected or not; 2. Where this titre is not precisely known but can be estimated through knowledge of the virus strains within the vaccine and in the field and of the performance of serological tests incorporating appropriate strains and standards; 3. In the absence of information on the correlation between serology results and protection where interpreting the serological response is limited to determining what proportion of animals have an antibody response that is consistent with successful vaccination (i.e. achieving the expected immunity targets). The vaccine quality, safety and efficacy of each batch of FMD vaccine should be guaranteed by the manufacturer (as described in Chapter 2.1.5, part C of the Terrestrial Manual, 2014). However, vaccine evaluation, independent of the manufacturer, can provide additional assurance of vaccine quality and strain suitability. It can also indicate the expected level of antibody to be found in animals at a known time after vaccination with a specific schedule and vaccine and measured using a particular test. This evaluation should ideally be carried out prior to wider use of the vaccine in the Foot and mouth disease vaccination and post-vaccination monitoring. Guidelines
