RT info:eu-repo/semantics/article T1 Broadly Cross-Reactive, Nonneutralizing Antibodies against Influenza B Virus Hemagglutinin Demonstrate Effector Function-Dependent Protection against Lethal Viral Challenge in Mice A1 Arunkumar, Guha Asthagiri A1 Ioannou, Andriani A1 Wohlbold, Teddy John A1 Meade, Philip A1 Aslam, Sadaf A1 Amanat, Fatima A1 Ayllón Barasoain, Juan A1 García Sastre, Adolfo A1 Krammer, Florian K1 ADCC K1 HA K1 Influenza B K1 MAb K1 Gripe K1 Influenza AB Protection from influenza virus infection is canonically associated with antibodies that neutralize the virus by blocking the interaction between the viral hemagglutinin and host cell receptors. However, protection can also be conferred by other mechanisms, including antibody-mediated effector functions. Here, we report the characterization of 22 broadly cross-reactive, nonneutralizing antibodies specific for influenza B virus hemagglutinin. The majority of these antibodies recognized influenza B viruses isolated over the period of 73 years and bind the conserved stalk domain of the hemagglutinin. A proportion of the characterized antibodies protected mice from both morbidity and mortality after challenge with a lethal dose of influenza B virus. Activity in an antibody-dependent cell-mediated cytotoxicity reporter assay correlated strongly with protection, suggesting that Fc-dependent effector function determines protective efficacy. The information regarding mechanism of action and epitope location stemming from our characterization of these antibodies will inform the design of urgently needed vaccines that could induce broad protection against influenza B viruses. PB American Society for Microbiology SN 0022-538X YR 2019 FD 2019-03 LK https://hdl.handle.net/10259/10928 UL https://hdl.handle.net/10259/10928 LA eng NO We thank Ariana Hirsh and Daniel Kaplan for excellent technical support. Andriani Ioannou was supported by an NIAID T32 Virus-Host Interactions training grant (5T32AI007647-17). This work was supported by NIAID grants R01 AI117287, U19 AI109946, and P01 AI097092 and the NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) contract HHSN272201400008C. The Krammer and García-Sastre labs are receiving funding for an unrelated influenza virus vaccine project from GlaxoSmithKline. DS Repositorio Institucional de la Universidad de Burgos RD 28-abr-2026