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Published on: March 24, 2017
Neutralization antigenic sites on type Asia-1 foot-and-mouth disease virus defined by monoclonal antibody-resistant
1Indian Veterinary Research Institute, Hebbal, Bangalore, India.
Abstract:
Seven neutralizing monoclonal antibodies (nMAbs) produced against serotype Asia-1 foot-and-mouth disease virus (FMDV) were used to select neutralization-resistant variants. Seven single and six multiple antibody-resistant variants were selected to identify neutralization antigenic sites on FMDV Asia-1. The variants no longer reacted with nMAbs which were used to select them when tested by microneutralization test (MNT), radioimmunoassay (RIA) and agar gel immunodiffusion (AGID) assay. Based on the binding and neutralization patterns of the variants, the nMAbs could be divided into discrete groups indicating the presence of three independent antigenic sites with evidence for occurrence of possibly a fourth site on the virus surface. Site 1 was present on 140S, 12Sps and VP1 and thus was conformation-independent. Sites 2 and 3 were restricted to the intact virion (140S) and thus were more conformation-dependent. Site 4 present on 140S virions and 12S protein subunits was less conformation-dependent. The site 3 nMAbs neutralized the infectivity of all the ten different Asia-1 virus isolates tested indicating that this site is conserved in Asia-1 virus serotype. Both cross-neutralization of different Asia-1 viruses with the nMAbs and cross-inhibition assays between MAbs demonstrated that the nMAbs recognized at least six different epitopes on Asia-1 virus.
Insights
Researchers identified three to four key antigenic sites on foot-and-mouth disease virus (FMDV) Asia-1 using neutralizing monoclonal antibodies (nMAbs). Site 3, recognized by nMAbs, is conserved across FMDV Asia-1 isolates, crucial for vaccine development.
Area of Science:
- Virology
- Immunology
- Structural Biology
Background:
- Foot-and-mouth disease virus (FMDV) poses a significant threat to livestock globally.
- Understanding FMDV antigenic sites is crucial for developing effective vaccines and control strategies.
- Serotype Asia-1 FMDV requires specific neutralization approaches.
Purpose of the Study:
- To identify and characterize neutralization antigenic sites on FMDV Asia-1.
- To investigate the conformational dependence of these antigenic sites.
- To assess the conservation of antigenic sites within the FMDV Asia-1 serotype.
Main Methods:
- Selection of neutralization-resistant FMDV Asia-1 variants using seven neutralizing monoclonal antibodies (nMAbs).
- Testing variant reactivity with nMAbs using microneutralization test (MNT), radioimmunoassay (RIA), and agar gel immunodiffusion (AGID).
- Analysis of nMAbs binding and neutralization patterns to define antigenic sites and epitopes.
Main Results:
- Seven single and six multiple antibody-resistant variants were successfully selected.
- nMAbs were categorized into groups, indicating three independent antigenic sites and possibly a fourth on the FMDV Asia-1 surface.
- Site 1 was conformation-independent (on 140S, 12Sps, VP1), Sites 2 and 3 were conformation-dependent (on 140S), and Site 4 was less conformation-dependent (on 140S, 12S).
- Site 3 nMAbs neutralized all ten tested Asia-1 virus isolates, demonstrating its conserved nature.
- Cross-neutralization and cross-inhibition assays revealed at least six distinct epitopes recognized by the nMAbs on FMDV Asia-1.
Conclusions:
- FMDV Asia-1 possesses at least three, possibly four, distinct neutralization antigenic sites.
- Site 3 is a conserved antigenic site across FMDV Asia-1 serotype, making it a promising target for vaccine development.
- The study elucidates the antigenic structure of FMDV Asia-1, aiding in the design of improved vaccines and diagnostic tools.
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