ABSTRACT
Evaluating how prior immunity to seasonal influenza viruses influences subsequent zoonotic influenza A virus (IAV) infection in animal models is critical for pandemic preparedness. In this study, we investigated the cross-protective effect of pre-existing A(H3N2) immunity in ferrets challenged with three distinct subtypes of zoonotic IAVs: low pathogenic A(H7N9) and A(H9N2) viruses, and highly pathogenic clade 2.3.4.4b A(H5N1) virus. Our results show that A(H3N2) preimmunity conferred some protection against A(H5N1) and A(H9N2) virus infection, as evidenced by more rapid viral clearance in the upper respiratory tract, reduced virus shedding in the nasal wash on select days post-inoculation, and a lowered frequency of viral detection in specific tissues compared with naive animals. In contrast, A(H3N2) preimmunity provided minimal cross-protection against A(H7N9) infection, as weight loss and viral dissemination in tissues were not significantly reduced in A(H3N2) preimmune ferrets relative to naive animals. These findings highlight the variable breadth and magnitude of cross-protection elicited by prior seasonal IAV immunity against zoonotic influenza virus challenges in the ferret model. Seasonal influenza A(H3N2) preimmunity provided differing levels of cross-protection against zoonotic influenza A virus infections in ferrets.
Source:
Link: https://journals.asm.org/doi/10.1128/spectrum.03974-25
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