Modeling Infectious Bursal Disease Virus (IBDV) Antigenic Drift In Vitro

Infectious bursal disease virus (IBDV) vaccines do not induce sterilizing immunity, and vaccinated birds can become infected with field strains. Vaccine-induced immune selection pressure drives the evolution of antigenic drift variants that accumulate amino acid changes in the hypervariable region (...

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Main Authors: Amin S. Asfor, Vishwanatha R. A. P. Reddy, Salik Nazki, Joanna Urbaniec, Andrew J. Brodrick, Andrew J. Broadbent
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/15/1/130
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author Amin S. Asfor
Vishwanatha R. A. P. Reddy
Salik Nazki
Joanna Urbaniec
Andrew J. Brodrick
Andrew J. Broadbent
author_facet Amin S. Asfor
Vishwanatha R. A. P. Reddy
Salik Nazki
Joanna Urbaniec
Andrew J. Brodrick
Andrew J. Broadbent
author_sort Amin S. Asfor
collection DOAJ
description Infectious bursal disease virus (IBDV) vaccines do not induce sterilizing immunity, and vaccinated birds can become infected with field strains. Vaccine-induced immune selection pressure drives the evolution of antigenic drift variants that accumulate amino acid changes in the hypervariable region (HVR) of the VP2 capsid, which may lead to vaccine failures. However, there is a lack of information regarding how quickly mutations arise, and the relative contribution different residues make to immune escape. To model IBDV antigenic drift in vitro, we serially passaged a classical field strain belonging to genogroup A1 (F52/70) ten times, in triplicate, in the immortalized chicken B cell line, DT40, in the presence of sub-neutralizing concentrations of sera from birds inoculated with IBDV vaccine strain 2512, to generate escape mutants. This assay simulated a situation where classical strains may infect birds that have suboptimal vaccine-induced antibody responses. We then sequenced the HVR of the VP2 capsid at passage (P) 5 and 10 and compared the sequences to the parental virus (P0), and to the virus passaged in the presence of negative control chicken serum that lacked IBDV antibodies. Two escape mutants at P10 had the same mutations, D279Y and G281R, and a third had mutations S251I and D279N. Furthermore, at P5, the D279Y mutation was detectable, but the G281R mutation was not, indicating the mutations arose with different kinetics.
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spelling doaj.art-d0f5f339d2f14d77a3a98f8e9241bdbb2023-12-01T01:10:47ZengMDPI AGViruses1999-49152022-12-0115113010.3390/v15010130Modeling Infectious Bursal Disease Virus (IBDV) Antigenic Drift In VitroAmin S. Asfor0Vishwanatha R. A. P. Reddy1Salik Nazki2Joanna Urbaniec3Andrew J. Brodrick4Andrew J. Broadbent5Birnaviruses Group, The Pirbright Institute, Ash Road, Woking GU24 0NF, UKBirnaviruses Group, The Pirbright Institute, Ash Road, Woking GU24 0NF, UKBirnaviruses Group, The Pirbright Institute, Ash Road, Woking GU24 0NF, UKBirnaviruses Group, The Pirbright Institute, Ash Road, Woking GU24 0NF, UKDepartment of Animal and Avian Sciences, College of Agriculture and Natural Resources, University of Maryland, College Park, MD 20742, USABirnaviruses Group, The Pirbright Institute, Ash Road, Woking GU24 0NF, UKInfectious bursal disease virus (IBDV) vaccines do not induce sterilizing immunity, and vaccinated birds can become infected with field strains. Vaccine-induced immune selection pressure drives the evolution of antigenic drift variants that accumulate amino acid changes in the hypervariable region (HVR) of the VP2 capsid, which may lead to vaccine failures. However, there is a lack of information regarding how quickly mutations arise, and the relative contribution different residues make to immune escape. To model IBDV antigenic drift in vitro, we serially passaged a classical field strain belonging to genogroup A1 (F52/70) ten times, in triplicate, in the immortalized chicken B cell line, DT40, in the presence of sub-neutralizing concentrations of sera from birds inoculated with IBDV vaccine strain 2512, to generate escape mutants. This assay simulated a situation where classical strains may infect birds that have suboptimal vaccine-induced antibody responses. We then sequenced the HVR of the VP2 capsid at passage (P) 5 and 10 and compared the sequences to the parental virus (P0), and to the virus passaged in the presence of negative control chicken serum that lacked IBDV antibodies. Two escape mutants at P10 had the same mutations, D279Y and G281R, and a third had mutations S251I and D279N. Furthermore, at P5, the D279Y mutation was detectable, but the G281R mutation was not, indicating the mutations arose with different kinetics.https://www.mdpi.com/1999-4915/15/1/130infectious bursal disease virus (IBDV)antigenic driftimmune escapeescape mutanthypervariable regionHVR
spellingShingle Amin S. Asfor
Vishwanatha R. A. P. Reddy
Salik Nazki
Joanna Urbaniec
Andrew J. Brodrick
Andrew J. Broadbent
Modeling Infectious Bursal Disease Virus (IBDV) Antigenic Drift In Vitro
Viruses
infectious bursal disease virus (IBDV)
antigenic drift
immune escape
escape mutant
hypervariable region
HVR
title Modeling Infectious Bursal Disease Virus (IBDV) Antigenic Drift In Vitro
title_full Modeling Infectious Bursal Disease Virus (IBDV) Antigenic Drift In Vitro
title_fullStr Modeling Infectious Bursal Disease Virus (IBDV) Antigenic Drift In Vitro
title_full_unstemmed Modeling Infectious Bursal Disease Virus (IBDV) Antigenic Drift In Vitro
title_short Modeling Infectious Bursal Disease Virus (IBDV) Antigenic Drift In Vitro
title_sort modeling infectious bursal disease virus ibdv antigenic drift in vitro
topic infectious bursal disease virus (IBDV)
antigenic drift
immune escape
escape mutant
hypervariable region
HVR
url https://www.mdpi.com/1999-4915/15/1/130
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