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Direct #airway delivery of a humanized anti - #H7N9 neutralizing #antibody broadly protects against divergent #H7 #influenza viruses in the mouse model

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By G.M.

 


ABSTRACT

Passive administration of broadly neutralizing anti-influenza monoclonal antibodies (mAbs) before or after virus infection can prevent or alleviate disease. Unlike seasonal influenza, infection with zoonotic avian influenza viruses can lead to acute respiratory distress syndrome and high mortality in humans. Respiratory tract-targeting antibody delivery appears to be more clinically relevant and effective for zoonotic influenza treatment. In this study, the efficacy of an anti-H7N9 murine mAb 4B7 and its humanized form (chi4B7) against H7 subtype influenza viruses administered through the intranasal route was investigated in mice. 4B7 recognizes critical residues in the vestigial esterase domain and receptor-binding sites in the hemagglutinin of H7N9 virus. The antibody had cross-H7 binding, hemagglutination inhibition, and neutralizing activities. In particular, the dose of 4B7 required for prophylactic protection against H7N9 infection was significantly reduced in mice treated locally (intranasal) compared with those treated systemically (intraperitoneal). Intranasal delivery of the antibody also enhanced therapeutic efficacy against H7N9 infection compared to intraperitoneal administration. Chi4B7 generated by grafting the variable regions onto the human IgG1 backbone sustained cross-reactivity with different H7 viruses of the parental murine antibody. Airway-delivered chi4B7 provided broad prophylactic and therapeutic protection against divergent H7 viruses in mice. Moreover, intranasal administration of chi4B7 had a long effective prophylaxis window against H7N9 infection. Our results suggest that airway delivery of the humanized anti-H7 antibody is a favorable approach for broad-spectrum prophylaxis and therapy against the H7 subtype influenza.

Source: 

Link: https://journals.asm.org/doi/10.1128/jvi.01327-25

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