Genetic stability (in vivo) of the attenuated oral rabies virus vaccine SAD B19

Abstract

The distribution of oral rabies vaccine baits containing replication-competent live viruses poses certain environmental safety risks; among others, the possibility of reversion to or an increase in virulence. Hence, the genetic stability of the complete genome of the most widely used oral rabies vaccine virus, SAD B19, was examined after four and 10 serial i.c. passages in foxes and mice, respectively. It was shown that the consensus strain of SAD B19 was extremely stable in vivo. After 10 consecutive passages in mice not a single mutation was observed. In foxes, seven single nucleotide exchanges were found between the first and fourth passage, of which only one resulted in an amino acid exchange at position 9240 of the L-gene. This mutation was not observed during the first three passages and, furthermore, it was shown that this mutation was not linked to enhanced virulence.

Genetic characterisation of the rabies virus vaccine strains used for oral immunization of foxes in Poland to estimate the effectiveness of vaccination

“…Homology at the level of 99.8–100 % was found between the SAD Bern and SAD B19 strains within 570-nt fragments of the N and G genes. This confirms the previously reported high conservation and genetic stability of SAD B19 strains passaged several times in mice [ 1 ]. It can be concluded that the virus strains used for production of oral vaccines, Fuchsoral and Lysvulpen, did not change during the years 1996–2014.…”

Molecular epidemiology of rabies virus in Poland

“…Although live attenuated oral rabies vaccines could revert to virulence and have low residual pathogenicity in certain rodents, it has been shown that they are safe for foxes, dogs and skunks [28, 29]. Intensive molecular investigation of SAD B19 strains passaged several times in mice has demonstrated their sequence conservation and genetic stability in vivo [2]. However, it should be considered that there is always a risk that the vaccine strain may revert to a fully pathogenic form, and thus, all rabies virus isolates collected from the field should be sequenced and subjected to phylogenetic analysis.…”

Relaxation of purifying selection on the SAD lineage of live attenuated oral vaccines for rabies virus

“…For example, attenuated live vaccines may show a pattern of relaxation of purifying selection, as was observed in three live attenuated vaccine strains of viruses belonging to the family Paramyxoviridae (Hughes 2009). In the case of the SAD vaccine strains, there have been reports of SAD vaccine-associated rabies in wildlife, in spite of evidence of the stability of the vaccine in experimental passaging studies (Beckert et al 2009). …”