Veterinary Sciences, Vol. 13, Pages 45: Highly Conserved Influenza A Nucleoprotein as a Target for Broad-Spectrum Intervention: Characterization of a Monoclonal Antibody with Pan-Influenza Reactivity


Veterinary Sciences, Vol. 13, Pages 45: Highly Conserved Influenza A Nucleoprotein as a Target for Broad-Spectrum Intervention: Characterization of a Monoclonal Antibody with Pan-Influenza Reactivity

Veterinary Sciences doi: 10.3390/vetsci13010045

Authors:
Jingrui Liu
Wenming Gao
Kunkun Zhao
Zongmei Huang
Lin Liu
Jingjing Chang
Xiaoyang Cao
Wenwen Zhou
Xiaojie Zhou
Yuman Liu
Xinsheng Li
Yapeng Song

Influenza A viruses remain a persistent global health challenge due to their rapid antigenic evolution, zoonotic potential, and pandemic threat. Universal countermeasures targeting conserved viral components are urgently needed to enhance diagnostic, surveillance, and therapeutic capabilities. Here, we report the generation and characterization of a high-affinity monoclonal antibody (2D8 mAb) against the nucleoprotein (NP) of the H9N2 avian influenza virus, a subtype with increasing relevance to human infections. Importantly, 2D8 mAb exhibited robust cross-reactivity with a broad spectrum of influenza A viruses, including H1, H3, H5, H7, and H9 subtypes, while showing no cross-reactivity with unrelated viral pathogens. Epitope mapping identified its binding target as a highly conserved NP motif 38RFYIQMCTEL47, which is invariant across all major human influenza A lineages. Isotyping revealed 2D8 mAb to be of the IgG2b/κ subclass, with an exceptionally high titer (1:20,480,000) as determined by ELISA. Given the essential role of NP in viral replication and host adaptation, this antibody offers a powerful platform for next-generation diagnostic assays capable of detecting a wide range of human and zoonotic influenza A viruses using a single reagent. Moreover, it holds potential for guiding the design of universal antiviral strategies targeting structurally constrained regions of the influenza virus. Our findings provide a valuable resource for advancing pan-influenza A interventions, with direct implications for improving pandemic preparedness and strengthening global influenza surveillance in both clinical and public health settings.



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Jingrui Liu www.mdpi.com