Live-attenuated rabies virus strains such as those derived from the field isolate Street Alabama Dufferin (SAD) have been used extensively and very effectively as oral
rabies vaccines for the control of fox
rabies in both Europe and Canada. Although these
vaccines are safe, some cases of
vaccine-derived
rabies have been detected during
rabies surveillance accompanying these campaigns. In recent analysis it was shown that some commercial SAD
vaccines consist of diverse viral populations, rather than clonal genotypes. For cases of
vaccine-derived
rabies, only consensus sequence data have been available to date and information concerning their population diversity was thus lacking. In our study, we used high-throughput sequencing to analyze 11 cases of
vaccine-derived
rabies, and compared their viral population diversity to the related oral
rabies vaccines using pairwise Manhattan distances. This extensive deep sequencing analysis of
vaccine-derived
rabies cases observed during oral vaccination programs provided deeper insights into the effect of accidental in vivo replication of genetically diverse
vaccine strains in the central nervous system of target and non-target species under field conditions. The viral population in
vaccine-derived cases appeared to be clonal in contrast to their parental
vaccines. The change from a state of high population diversity present in the
vaccine batches to a clonal genotype in the affected animal may indicate the presence of a strong bottleneck during
infection. In conclusion, it is very likely that these few cases are the consequence of host factors and not the result of the selection of a more virulent genotype. Furthermore, this type of
vaccine-derived
rabies leads to the selection of clonal genotypes and the selected variants were genetically very similar to potent SAD
vaccines that have undergone a history of in vitro selection.