Abstract

Outbreaks of avian infectious bronchitis virus (IBV) often occur in vaccinated flocks. The antibody-dependent enhancement (ADE) has been proposed as a potential mechanism underlying coronavirus vaccine failure. However, this hypothesis has yet to be substantiated in flocks. This study demonstrates ADE occurrence in IBV (gamacoronavirus) in vitro and in vivo. Using the SPF chicken host model, primary infection with an O-glycosylation-modified attenuated strain enhanced pathogenesis upon secondary homologous/heterologous virulent challenge, increasing morbidity/mortality (≥30%), pathological lesions, and viral loads. Notably, sequentially attenuated infections also induced ADE, suggesting live attenuated vaccine risks. The immune serum raised against the O-glycosylation-modified attenuated strain was also pre-mixed with the challenge strain, and the mixtures were then inoculated into target cells, non-susceptible macrophage cells, or a co-culture of both cell types. The serum-virus complexes replicated poorly in macrophages, yet immune cells amplified the expression of inflammatory factors and ADE-mediated viral replication in target cells, indicating a significant promoting role of immune cells in this process. The concentrations of complement component C3 and neutralizing antibodies in the immune serum were also measured, and results showed that the induction of this ADE is associated with high complement component C3 and low neutralizing antibody titers. These findings highlight risks for vaccines and antibody-based therapeutic strategies of coronavirus infection.

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