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

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.

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Antiviral potential of ivermectin against foot-and-mouth disease virus, serotype O, A and Asia-1

Microbial Pathogenesis ◽

10.1016/j.micpath.2021.104914 ◽

2021 ◽

pp. 104914

Author(s):

Zahra Naeem ◽

Sohail Raza ◽

Saba Afzal ◽

Ali Ahmad Sheikh ◽

Muhammad Muddassir Ali ◽

...

Keyword(s):

Disease Virus ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Serotype O ◽

Mouth Disease Virus ◽

Virus Serotype ◽

Foot And Mouth

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Novel antibody binding determinants on the capsid surface of serotype O foot-and-mouth disease virus

Journal of General Virology ◽

10.1099/vir.0.060939-0 ◽

2014 ◽

Vol 95 (5) ◽

pp. 1104-1116 ◽

Cited By ~ 19

Author(s):

Amin S. Asfor ◽

Sasmita Upadhyaya ◽

Nick J. Knowles ◽

Donald P. King ◽

David J. Paton ◽

...

Keyword(s):

Amino Acid ◽

Guinea Pig ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Amino Acid Residues ◽

Serotype O ◽

Antigenic Sites ◽

Mouth Disease Virus ◽

Foot And Mouth ◽

The Impact

Five neutralizing antigenic sites have been described for serotype O foot-and-mouth disease viruses (FMDV) based on monoclonal antibody (mAb) escape mutant studies. However, a mutant virus selected to escape neutralization of mAb binding at all five sites was previously shown to confer complete cross-protection with the parental virus in guinea pig challenge studies, suggesting that amino acid residues outside the mAb binding sites contribute to antibody-mediated in vivo neutralization of FMDV. Comparison of the ability of bovine antisera to neutralize a panel of serotype O FMDV identified three novel putative sites at VP2-74, VP2-191 and VP3-85, where amino acid substitutions correlated with changes in sero-reactivity. The impact of these positions was tested using site-directed mutagenesis to effect substitutions at critical amino acid residues within an infectious copy of FMDV O1 Kaufbeuren (O1K). Recovered viruses containing additional mutations at VP2-74 and VP2-191 exhibited greater resistance to neutralization with both O1K guinea pig and O BFS bovine antisera than a virus that was engineered to include only mutations at the five known antigenic sites. The changes at VP2-74 and VP3-85 are adjacent to critical amino acids that define antigenic sites 2 and 4, respectively. However VP2-191 (17 Å away from VP2-72), located at the threefold axis and more distant from previously identified antigenic sites, exhibited the most profound effect. These findings extend our knowledge of the surface features of the FMDV capsid known to elicit neutralizing antibodies, and will improve our strategies for vaccine strain selection and rational vaccine design.

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

Journal of General Virology ◽

10.1099/vir.0.032839-0 ◽

2011 ◽

Vol 92 (10) ◽

pp. 2297-2309 ◽

Cited By ~ 26

Author(s):

F. F. Maree ◽

B. Blignaut ◽

J. J. Esterhuysen ◽

T. A. P. de Beer ◽

J. Theron ◽

...

Keyword(s):

South African ◽

Disease Virus ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Sub Saharan Africa ◽

Antigenic Sites ◽

Mouth Disease Virus ◽

Virus Serotype ◽

Antigenic Properties ◽

Foot And Mouth

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 r1-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 r1-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.

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