A recombinant Newcastle disease virus-vectored multi-epitope vaccine confers protection against QX-like infectious bronchitis virus in chickens.

Infectious bronchitis virus (IBV) QX-like (GI-19) genotype dominates global poultry flocks, yet Mass-type vaccines fail to confer cross-protection. We developed a recombinant Newcastle disease virus (NDV) LaSota vector expressing conserved IBV S1 B-cell hotspots paired with S1-derived BF2-restricted CTL epitopes (rNDV-IBV-T/B). Specific-pathogen-free chickens received single or booster ocular-nasal immunization (106 EID50) followed by QX-like challenge. Booster immunization increased the frequency of splenic CD3+CD8+ T cells (41.3% vs. 31.9% in the sham-vaccinated challenge control; Tukey-adjusted p<0.001) and elicited neutralizing antibodies (peak log2 GMT, 5.80). Vaccinated groups showed markedly reduced clinical scores, preserved tracheal ciliary activity at all assessed post-challenge time points, and mitigated histopathological lesions. Vaccination reduced oropharyngeal and cloacal viral RNA shedding at multiple post-challenge time points, with the booster regimen producing a more consistent reduction in cloacal viral RNA. Protection was accompanied by an increased frequency of splenic CD3+CD8+ T cells, particularly after booster immunization, suggesting a role for cellular immunity alongside neutralizing antibodies. The NDV-LaSota backbone functions as a modular platform for rapid vaccine redesign against emerging coronavirus variants.