Evidence for more than one important, neutralizing site on foot-and-mouth disease virus

Thomas, Adrianus; Woortmeijer, R J; Barteling, S. J.; Meloen, Rob H.

doi:10.1007/bf01311072

Cited by 28 publications

(12 citation statements)

References 15 publications

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“…MAbs have been used extensively to identify several antigenic sites on the structural proteins of virions belonging to serotypes A (15)(16)(17), O (13,18), C (19), and Asia-1 (20). Not surprisingly, these antigenic sites were located on structural protrusions on the virus surface, formed mainly by the loops connecting ␤-barrel structures of the three outer capsid proteins.…”

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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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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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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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“…This was supported by the fact that animals with low levels of neutralizing antibodies could also be protected [34-37]. A broad repertoire of epitope specificities following vaccination has been observed in previous studies [38,39]. Also, Nagendrakumar [33] have reported that the hyperimmune sera collected from vaccinated animals were unable to compete with the panel of mAbs used in their study.…”

Section: Discussionmentioning

confidence: 69%

Characterization of monoclonal antibodies against foot-and-mouth disease virus serotype O and application in identification of antigenic variation in relation to vaccine strain selection

Yang

Goolia

et al. 2014

Virol J

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BackgroundFoot-and-mouth disease (FMD) has severe implications for animal farming which leads to considerable financial losses because of its rapid spread, high morbidity and loss of productivity. For these reasons, the use of vaccine is often favoured to prevent and control FMD. Selection of the proper vaccine is extremely difficult because of the antigenic variation within FMDV serotypes. The aim of the current study was to produce a panel of mAbs and use it for the characterization of new isolates of FMDV serotype O.ResultsA panel of FMDV/O specific mAb was produced. The generated mAbs were then characterized using the peptide array and mAb resistant mutant selection. Seven out of the nine mAbs reacted with five known antigenic sites, thus the other two mAbs against non-neutralizing sites were identified. The mAbs were then evaluated by antigenic ELISA for the detection of forty-six FMDV serotype O isolates representing seven of ten known topotypes. Isolates ECU/4/10 and HKN/2/11 demonstrated the highest antigenic variation compared to the others. Furthermore, the panel of mAbs was used in vaccine matching by antigenic profiling ELISA with O1/Manisa as the reference strain. However, there was no correlation between vaccine matching by antigenic ELISA and the gold standard method, virus neutralisation test (VNT), for the forty-six FMDV/O isolates. Nine isolates had particularly poor correlation with the reference vaccine strain as revealed by the low r1 values in VNT. The amino acid sequences of the outer capsid proteins for these nine isolates were analyzed and compared with the vaccine strain O1/Manisa. The isolate ECU/4/10 displayed three unique amino acid substitutions around the antigenic sites 1, 3 and 4.ConclusionsThe panel of mAbs is useful to monitor the emergence of antigenically different strains and determination of relevant antigenic site differences. However, for vaccine matching VNT remains the preferred method but a combination of VNT, antigenic profiling with a panel of mAbs and genetic sequencing would probably be more ideal for full characterization of any new outbreak isolates as well as for selection of vaccine strains from FMDV antigen banks.

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“…However, a potential problem with this approach is that antibody bound to one site may interfere with a competitive ligand targeted elsewhere on the virus surface, due to the small size of the virion and close vicinity of different antigenic sites. Other studies involving serotype C (Mateu et al , 1995) and serotype A (Thomas et al , 1988b) also indicated the participation of other antigenic sites in addition to site 1 in generation of an immune response following either natural infection or vaccination.…”

Section: Full Textmentioning

confidence: 98%

Foot-and-mouth disease virus epitope dominance in the antibody response of vaccinated animals

Mahapatra

Hamblin

Paton

2012

Journal of General Virology

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Five neutralizing antigenic sites have been identified on the surface of serotype O foot-and-mouth disease virus (FMDV). A set of mAb neutralization-escape mutant viruses was used for the first time to evaluate the relative use of known binding sites by polyclonal antibodies from three target species: cattle, sheep and pigs. Antibodies to all five neutralizing antigenic sites were detected in all three species, with most antibodies directed against antigenic site 2, followed by antigenic site 1. In 76 % of cattle, 65 % of sheep and 58 % of pigs, most antibodies were directed against site 2. Antibodies specific to antigenic sites 3, 4 and 5 were found to be minor constituents in the sera of each of the target species. This implies that antigenic site 2 is a dominant neutralization immunogenic site in serotype O FMDV and may therefore be a good candidate for designing novel vaccines.Foot-and-mouth disease (FMD) is a severe, clinically acute vesicular disease of cloven-hoofed domestic and wild animals and is present in all continents except Australasia and North America. The causative agent of FMD is Footand-mouth disease virus (FMDV), the prototype member of the genus Aphthovirus in the family Picornaviridae. There are seven distinct serotypes of FMDV (O, A, C, Asia-1, SAT-1, SAT-2 and SAT-3) and multiple strains, indicating significant antigenic variability. Currently, immunization with conventional inactivated whole-virus vaccine is the main method of FMD control, but strain composition of vaccines must be selected with care. The humoral immune response has been generally accepted as the most important factor in conferring vaccine-induced protection against the disease, as a strong correlation has been reported between the levels of virus-neutralizing antibody produced after vaccination and subsequent protection of cattle, one of the main target species (Pay & Hingley, 1987). The mechanism by which antibodies protect against FMDV is poorly understood, and different factors may be involved in vivo compared with the situation measured in vitro (Dunn et al., 1998;McCullough et al., 1992). Several studies have been carried out in the last two decades to identify the targets on the virus surface for the binding of neutralizing antibodies, and mAbs have been powerful tools for identifying the amino acid footprint of different antigenic sites, mainly by sequencing mAb-resistant (mar) mutants. This approach has been used successfully to delineate the neutralizing antigenic sites of viruses representing serotypes O (Aktas & Samuel, 2000;Barnett et al., 1998;Crowther et al., 1993b), A (Baxt et al., 1989;Bolwell et al., 1989;Mahapatra et al., 2011;Thomas et al., 1988a), C (Mateu et al., 1990, Asia-1 (Grazioli et al., 2003) and SAT (Crowther et al., 1993a; Grazioli et al., 2006). FMDV serotype O is the most prevalent globally and has been studied most extensively. Five neutralizing antigenic sites (1-5), involving three of the capsid proteins (VP1-3), have been identified on the surface of serotype O FMDV (Aktas & Samue...

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Evidence for more than one important, neutralizing site on foot-and-mouth disease virus

Abstract: Using polyclonal sera raised against foot-and-mouth disease virus in susceptible animals, evidence was obtained for the existence of at least one further important antigenic site in addition to the neutralizing site on VP1 140-160.

Cited by 28 publications

References 15 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

Characterization of monoclonal antibodies against foot-and-mouth disease virus serotype O and application in identification of antigenic variation in relation to vaccine strain selection

Foot-and-mouth disease virus epitope dominance in the antibody response of vaccinated animals

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