Integrated molecular and pathobiological evaluation of three live Infectious Bursal Disease vaccines reveals differential replication, immunogenicity and genetic stability.

Authors

Jan Mohd Muneeb, Irfan Gul, Amreena Hassan, Towseef Akram, Basharat Maqbool Wani, Azmat Alam Khan, Zulfqarul Haq, Shayaib Ahmad Kamil, Riaz Ahmad Shah, Syed Mudasir Ahmad, Nazir Ahmad Ganai, Naveed Anjum Chikan, Mohammad Faizal Abdul Careem, Nadeem Shabir

Published in

Avian pathology : journal of the W.V.P.A. Pages 1-34. Jun 22, 2026. Epub Jun 22, 2026.

Abstract

Live-attenuated vaccines are widely used for prevention and control of Infectious Bursal Disease (IBD) in poultry, yet differences in attenuation, replication and immunogenicity among vaccines remain incompletely characterised. This study comparatively evaluated three live-attenuated IBDV vaccines (Vaccine-A, Vaccine-B and Vaccine-C) using integrated molecular, pathobiological and immunological analyses. Molecular analysis using next-generation sequencing revealed that all vaccines possessed canonical attenuation-associated substitutions (253H, 279N and 284 T) in the VP2 hypervariable region, but differed in additional lineage- and virulence-associated residues. Vaccine-A retained several residues characteristic of very virulent IBDV (vvIBDV), including 222A, 242I, 256I, 294I and 299S, whereas Vaccines-B and -C displayed mixed classical and vvIBDV-associated profiles. Notably, Vaccine-C contained a vvIBDV-derived VP1 polymerase. These molecular differences corresponded to distinct in vivo phenotypes. Vaccine-C showed higher and more persistent vaccine-viral RNA levels in the bursa of Fabricius, with greater lymphoid depletion and lesion severity. In contrast Vaccine-A exhibited lower residual viral RNA levels and milder pathology. All vaccines induced homologous and cross-neutralising antibody responses, although response kinetics differed. Vaccine-A elicited earlier cross-neutralising responses, while Vaccine-C generated higher peak titres at later time points. Cytokine profiling showed stronger pro-inflammatory signals with Vaccine-C and higher early type-I interferon expression with Vaccine-A. Under selective pressure in DT-40 cells, Vaccine-A lost vvIBDV-associated residues, Vaccine-B accumulated substitutions including N279D, whereas Vaccine-C exhibited moderate VP2 variability. Overall, these findings suggest that vaccine molecular composition may influence viral replication, tissue pathology and immune responses, with Vaccine-A demonstrating a relatively favourable balance between safety and immunogenicity under the present experimental conditions.

PMID:
42324932
Bibliographic data and abstract were imported from PubMed on 22 Jun 2026.

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