Classical swine fever (CSF) continues to be the most economically damaging pig disease in the world. The disease can be effectively controlled by vaccination with the live C-strain vaccine. This vaccine, however, does not enable the serological differentiation between infected and vaccinated animals (DIVA) and its use can therefore impose severe trade restrictions. CSF-specific diagnostic ELISAs detect antibodies directed against the conserved and immunodominant A domain of the E2 structural glycoprotein. We previously reported the production of a C-strain virus in which the immunodominant TAVSPTTLR epitope of the A domain is stably mutated with the aim to render the virus suitable as a DIVA vaccine. We here report that a single vaccination with this vaccine virus protected pigs from a lethal challenge dose of the highly virulent Brescia strain. Analysis of the sera, however, demonstrated that a commercially available E2 ELISA was unsuitable as an accompanying DIVA test.
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