A Safe Foot-and-Mouth Disease Vaccine Platform with Two Negative Markers for Differentiating Infected from Vaccinated Animals

Use of recombinant capsid proteins in the development of a vaccine against the foot-and-mouth disease virus

“…It is well known that interferon has a strong inhibitory effect on FMDV replication and studies have shown that expression of interferon, from adenovirus vectors, can effectively block FMDV replication in swine. 71 The precise deletion of the Lb coding region to make a socalled "leaderless virus" (see Figure 4) from FMDV results in a virus which is still viable [72][73][74] but attenuated in cattle. 75 The loss of Lb results in a decreased ability of the virus to shut off host cell protein synthesis; this will allow the synthesis of interferon.…”

Influence of the Leader protein coding region of foot-and-mouth disease virus on virus replication

“…No simple transition or transversion events were detected that modified the Lab initiation codon or, alternatively, introduced a stop codon within the 'spacer' region, although it is not essential to retain the Lab initiation codon for virus viability since it could be modified, as in the O1KDLbAUGmut virus. There are no indications of modification of this region within the A12LLV2 or A24LL viruses (Piccone et al, 1995;Uddowla et al, 2012), but the utilization of the two initiation sites can vary between different virus strains and if there is a stronger bias towards the use of the second site then the selection pressure will be less. The results reported here are consistent with earlier studies, using reporter gene constructs, which indicated that the presence of frameshift mutations within the 'spacer' region did not affect utilization of the Lb initiation codon (Ló pez de Quinto & Martínez-Salas, 1999).…”

“…2 of Piccone et al, 1995). In contrast, the A24LL derivative, lacking Lb, grew with similar kinetics to the parental A24 virus but the capsid proteins produced by these viruses were not compared (Uddowla et al, 2012).…”

“…The same strategy was used in the recent studies by Uddowla et al (2012) using the A24 strain of virus. In principle, these mutant viruses should produce two forms of the P1-2A capsid precursor.…”

“…Thus, the presence of the Lab start site, in addition to the Lb start site, could compromise the viability of the mutant FMD viruses lacking Lb alone. However, it is clear that this is not a total block since viruses of this form were obtained (Piccone et al, 1995;Uddowla et al, 2012). The A12LLV2 virus grows much more slowly than the wt A12 virus and an extended form of the VP0 protein (produced by 3C pro mediated processing of the P1-2A precursor) from the LLV2 derivative of the A12 virus was apparent in addition to the authentic VP0 product (see Fig.…”