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

Opperman, Pamela Anne; Maree, Francois Frederick; Wyngaardt, Wouter Van; Vosloo, Wilna; Theron, Jacques

doi:10.1016/j.virusres.2012.05.026

Cited by 10 publications

(19 citation statements)

References 73 publications

(48 reference statements)

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“…1). Residues 144 to 154 and 210 of VP1, all of which fall within previously identified SAT2 antigenic regions (23,25,26), were conserved between SAT2/ZIM/7/83 and SAT2/KNP/19/89. (28).…”

Section: Prediction Of Antigenic Sites On the Sat2 Fmd Capsidmentioning

confidence: 61%

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Determining the Epitope Dominance on the Capsid of a Serotype SAT2 Foot-and-Mouth Disease Virus by Mutational Analyses

Opperman

Rotherham

Esterhuysen

et al. 2014

J Virol

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Monoclonal-antibody (MAb)-resistant mutants were used to map antigenic sites on foot-and-mouth disease virus (FMDV), which resulted in the identification of neutralizing epitopes in the flexible ␤G-␤H loop in VP1. For FMDV SAT2 viruses, studies have shown that at least two antigenic sites exist. By use of an infectious SAT2 cDNA clone, 10 structurally exposed and highly variable loops were identified as putative antigenic sites on the VP1, VP2, and VP3 capsid proteins of SAT2/Zimbabwe (ZIM)/ 7/83 (topotype II) and replaced with the corresponding regions of SAT2/Kruger National Park (KNP)/19/89 (topotype I). Virus neutralization assays using convalescent-phase antisera raised against the parental virus, SAT2/ZIM/7/83, indicated that the mutant virus containing the TQQS-to-ETPV mutation in the N-terminal part of the ␤G-␤H loop of VP1 showed not only a significant increase in the neutralization titer but also an increase in the index of avidity to the convalescent-phase antisera. Furthermore, antigenic profiling of the epitope-replaced and parental viruses with nonneutralizing SAT2-specific MAbs led to the identification of two nonneutralizing antigenic regions. Both regions were mapped to incorporate residues 71 to 72 of VP2 as the major contact point. The binding footprint of one of the antigenic regions encompasses residues 71 to 72 and 133 to 134 of VP2 and residues 48 to 50 of VP1, and the second antigenic region encompasses residues 71 to 72 and 133 to 134 of VP2 and residues 84 to 86 and 109 to 11 of VP1. This is the first time that antigenic regions encompassing residues 71 to 72 of VP2 have been identified on the capsid of a SAT2 FMDV. IMPORTANCEMonoclonal-antibody-resistant mutants have traditionally been used to map antigenic sites on foot-and-mouth disease virus (FMDV). However, for SAT2-type viruses, which are responsible for most of the FMD outbreaks in Africa and are the most varied of all seven serotypes, only two antigenic sites have been identified. We have followed a unique approach using an infectious SAT2 cDNA genome-length clone. Ten structurally surface-exposed, highly varied loops were identified as putative antigenic sites on the VP1, VP2, and VP3 capsid proteins of the SAT2/ZIM/7/83 virus. These regions were replaced with the corresponding regions of an antigenically disparate virus, SAT2/KNP/19/89. Antigenic profiling of the epitope-replaced and parental viruses with SAT2-specific MAbs led to the identification of two unique antibody-binding footprints on the SAT2 capsid. In this report, evidence for the structural engineering of antigenic sites of a SAT2 capsid to broaden cross-reactivity with antisera is provided. Genetically modified viruses provide a valuable tool for the manipulation of the biological properties of field and laboratory strains and present a promising avenue for the design of safe and effective vaccines. The modification of antigenic regions of human immunodeficiency virus (HIV) by amino acid (aa) substitutions in a recombinant virus has been used to confirm m...

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“…1). Residues 144 to 154 and 210 of VP1, all of which fall within previously identified SAT2 antigenic regions (23,25,26), were conserved between SAT2/ZIM/7/83 and SAT2/KNP/19/89. (28).…”

Section: Prediction Of Antigenic Sites On the Sat2 Fmd Capsidmentioning

confidence: 61%

“…The antigenic site located in the ␤G-␤H loop of VP1, downstream of the RGD motif, at residues 147, 148, 156, and 158 (25), residue 154 (23), and residue 159 (26) is analogous to site 1 of serotype O 1 BFS (13). Residue 79 of VP2 may also play a role in forming this antigenic site; however, the role of residue 79 in site 1 remains unclear (23).…”

mentioning

confidence: 99%

Determining the Epitope Dominance on the Capsid of a Serotype SAT2 Foot-and-Mouth Disease Virus by Mutational Analyses

Opperman

Rotherham

Esterhuysen

et al. 2014

J Virol

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“…The SAT2 FMDV vaccine strain Zimbabwe (ZIM)/7/83 is a bovine virus originating from an outbreak in western Zimbabwe during 1983 [35] and was maintained at the Transboundary Animal Diseases (TAD) of the Agricultural Research Council (ARC) (South Africa). The plasmid pSAT2, a genome-length infectious cDNA clone of SAT2/ZIM/7/83 [36], was used as the genetic backbone in the construction of recombinant cDNA clones with amino acid substitutions S2093Y and S2093H in VP2 [20].…”

Section: Cells Viruses and Plasmidsmentioning

confidence: 99%

Evaluation of immune responses of stabilised SAT2 antigens of foot-and-mouth disease in cattle

Scott

Rathogwa

Capozzo³

et al. 2017

Vaccine

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“…To develop more effective vaccines or peptide vaccines, numerous FMDV studies have been undertaken to identify these neutralizing antigenic sites in more detail (14). Neutralizing antigenic sites have been identified for serotype A (15)(16)(17), O (18)(19)(20)(21), C (22), Asia-1 (23), and SAT2 (19,24,25). However, information regarding the antigenic determinants of SAT serotypes, which are confined geographically to Africa, is scarce (26).…”

Section: Introductionmentioning

confidence: 99%

“…However, information regarding the antigenic determinants of SAT serotypes, which are confined geographically to Africa, is scarce (26). Mapped SAT2 epitopes include: (i) βG-βH loop of VP1; (ii) residue 210 in the C-terminus of VP1; (iii) VP1 84-86, 109-111, VP2 71,72,133,134; and (iv) VP1 159, VP2 71-72, 133-134, 148-150 (19,24,25,27,28). Four independent antigenic determinants were identified for SAT1 viruses i.e., (i) two occurring in the βG-βH loop of VP1; (ii) two simultaneous residues one in VP3 (position 135 or 71 or 76) and one in VP1 (position 179 or 181); (iii) a conformation dependant site Abbreviations: FMD, foot-and-mouth disease; FMDV, FMD virus; scFv, singlechain variable fragment; MAb, monoclonal antibody.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic and Epitope Mapping Potential of Single-Chain Antibody Fragments Against Foot-and-Mouth Disease Virus Serotypes A, SAT1, and SAT3

et al. 2020

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

Cited by 10 publications

References 73 publications

Determining the Epitope Dominance on the Capsid of a Serotype SAT2 Foot-and-Mouth Disease Virus by Mutational Analyses

Determining the Epitope Dominance on the Capsid of a Serotype SAT2 Foot-and-Mouth Disease Virus by Mutational Analyses

Evaluation of immune responses of stabilised SAT2 antigens of foot-and-mouth disease in cattle

Diagnostic and Epitope Mapping Potential of Single-Chain Antibody Fragments Against Foot-and-Mouth Disease Virus Serotypes A, SAT1, and SAT3

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