Predicting antigenic sites on the foot-and-mouth disease virus capsid of the South African Territories types using virus neutralization data

Abstract

Foot-and-mouth disease virus (FMDV) outer capsid proteins 1B, 1C and 1D contribute to the virus serotype distribution and antigenic variants that exist within each of the seven serotypes. This study presents phylogenetic, genetic and antigenic analyses of South African Territories (SAT) serotypes prevalent in sub-Saharan Africa. Here, we show that the high levels of genetic diversity in the P1-coding region within the SAT serotypes are reflected in the antigenic properties of these viruses and therefore have implications for the selection of vaccine strains that would provide the best vaccine match against emerging viruses. Interestingly, although SAT1 and SAT2 viruses displayed similar genetic variation within each serotype (32 % variable amino acids), antigenic disparity, as measured by r 1 -values, was less pronounced for SAT1 viruses compared with SAT2 viruses within our dataset, emphasizing the high antigenic variation within the SAT2 serotype. Furthermore, we combined amino acid variation and the r 1 -values with crystallographic structural data and were able to predict areas on the surface of the FMD virion as antigenically relevant. These sites were mostly consistent with antigenic sites previously determined for types A, O and C using mAbs and escape mutant studies. Our methodology offers a quick alternative to determine antigenic relevant sites for FMDV field strains.

Intra-serotype SAT2 chimeric foot-and-mouth disease vaccine protects cattle against FMDV challenge

“…The fact that the viral RNA can be made infectious in the absence of other components of the virion (reverse genetics) opened the theoretical possibility of genetically engineer-ing new viruses from in vitro-generated RNA molecules [24,27]. The introduction of specific mutations into the cloned genomes of viruses has allowed the manipulation of the biological prop-erties of field and laboratory strains and presents a promising avenue for the design of safe and effective vaccines [28][29][30]. We have structurally-engineered recombinant SAT viruses, containing desirable antigenic determinants and cell adaptation phenotypes [28,31,32] providing the proof-of-concept to rationally design viruses with the desired biological properties of a good vaccine strain.…”

“…The introduction of specific mutations into the cloned genomes of viruses has allowed the manipulation of the biological prop-erties of field and laboratory strains and presents a promising avenue for the design of safe and effective vaccines [28][29][30]. We have structurally-engineered recombinant SAT viruses, containing desirable antigenic determinants and cell adaptation phenotypes [28,31,32] providing the proof-of-concept to rationally design viruses with the desired biological properties of a good vaccine strain. Several studies have shown that inter-serotype chimeric vaccines successfully induce protective immune responses and protect FMD host species against live virus challenge [26,30,33].…”

“…The intra-serotype vaccine was prepared from a chimeric virus containing the external capsid-coding region of a field SAT2 isolate, ZIM/14/90, inserted in the genetic background of a SAT2 infectious clone [34]. The SAT2/ZIM/14/90 virus was iso-lated from buffalo which originated from Doma Safari area (16 • 20 , 30 • 15 ) in Zimbabwe and was selected for its potential use as a vaccine strain based on (i) initial data showing the ability to elicit an immune response that cross-reacts broadly against the three SAT2 topotype viruses from southern Africa [28] and (ii) the 9.7%amino acid differences in the capsid proteins compare to the SAT2 infectious clone shows genetic divergence from the clone [28].…”

Crystal structure of the 3C protease from South African Territories type 2 foot-and-mouth disease virus

“…This is because the vaccines provide only short-lived protection and the virus occurs as seven clinically indistinguishable serotpyes (O, A, C, Asia1 and three South African Territories serotypes: SAT1, SAT2 and SAT3), each of which has multiple, constantly evolving sub-types (Knowles & Samuel, 2003). Viruses belonging to the SAT serotypes display appreciably greater genomic and antigenic variation compare to serotype A and O viruses (Bastos et al, 2001;Bastos et al, 2003;Maree et al 2011), possibly due to their long term maintenance within African buffalo (Syncerus caffer). Constant surveillance of circulating strains is required to ensure that vaccine stocks remain effective.…”

Mapping of antigenic determinants on a SAT2 foot-and-mouth disease virus using chicken single-chain antibody fragments

“…The antigenic sites Ia and Ib of SAT1 viruses, for example, involve residues on both sides of the RGD motif in the G-H loop (Grazioli et al, 2006). In addition, plotting the observed variant amino acid residue on a model of the capsid pentamer of ZIM/7/83 indicated that the proposed epitope would be surface exposed and this position coincides with an antigenic region predicted by Reeve et al (2010) and Maree et al (2011) on ZIM/7/83. Added to this, the region has previously been identified as an antigenic area in the SAT2 viruses RHO/1/48 (Crowther et al, 1993b), as well as in ZIM/5/81 (Grazioli et al, 2006).…”