A neuraminidase specific monoclonal antibody delays highly pathogenic H5N1 influenza viral burden 3648

Abstract Description Monoclonal antibodies (mAbs) were cloned from an individual following seasonal quadrivalent inactivated influenza vaccine. One mAb (1090F12) was found to broadly bind N1 neuraminidase ranging from A/Brevig Mission/1/1918 (H1N1) to A/Cambodia/NPH230032_2/2023 (H5N1). 1090F12 inhibited neuraminidase activity in an ELLA assay but did not inhibit neuraminidase in MUNANA assay suggesting that it does not directly bind the active site but rather outside at an epitope obscuring the active site. 1090F12 bound and neutralized the recent H5N1 human isolate A/Texas/37/2024 in vitro. Notably,1090F12 administered both 6 hours prior and 2 days after challenge with A/Texas/37/2024 reduced visible viral load through 8 dpi compared to IgG control mice. All IgG control treated mice were euthanized by 9 dpi, however body weight declined in 1090F12 mice and 60% were euthanized by 10 dpi demonstrating that 1090F12 delayed outcomes of infection and increased survival following H5N1 infection. Continuing efforts will elucidate the structural binding characteristics and refine therapeutic effects of 1090F12. These results suggest that a subset of N1 antibodies induced by seasonal influenza quadrivalent inactivated influenza vaccine have the potential to control H5N1 infection. Funding Sources Supported by NIH 5R01AI145332. Topic Categories Vaccines and Immunotherapy (VAC)