A potent broad-spectrum protective human monoclonal antibody crosslinking two haemagglutinin monomers of influenza A virus
By Ying Wu, M. Cho, D. Shore, M. Song, Jung-ah Choi, T. Jiang, Yongqiang Deng, M. Bourgeois, L. Almli, Hua Yang and 15 more. 2015
139 citations recorded by the source corpus.
Effective annual influenza vaccination requires frequent changes in vaccine composition due to both antigenic shift for different subtype hemagglutinins (HAs) and antigenic drift in a particular HA. Here we present a broadly neutralizing human monoclonal antibody with an unusual binding modality. The antibody, designated CT149, was isolated from convalescent patients infected with pandemic H1N1 in 2009. CT149 is found to neutralize all tested group 2 and some group 1 influenza A viruses by inhibiting low pH-induced, HA-mediated membrane fusion. It promotes killing of infected cells by Fc-mediated antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. X-ray crystallographic data reveal that CT149 binds primarily to the fusion domain in HA2, and the light chain is also largely involved in binding. The epitope recognized by this antibody comprises amino-acid residues from two adjacent protomers of HA. This binding characteristic of CT149 will provide more information to support the design of more potent influenza vaccines. Monoclonal antibodies with broadly neutralizing activity are being developed as potential treatment of influenza infections. Here, the authors describe a broadly neutralizing antibody with an unusual mode of binding to viral haemagglutinin, which has been isolated from patients convalescent from pandemic H1N1 influenza infection.
Subfields: Epidemiology, Radiology, Nuclear Medicine and Imaging
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Epidemiology
In Radiology, Nuclear Medicine and Imaging
Citations in the corpus
- Design of Nanoparticulate Group 2 Influenza Virus Hemagglutinin Stem Antigens That Activate Unmutated Ancestor B Cell Receptors of Broadly Neutralizing Antibody Lineages (2018, unknown): “One candidate displaying H1-based HA stem trimers on self-assembling ferritin nanoparticles protected mice and ferrets from a lethal heterosubtypic H5N1 influenza challenge (17).”
- Glycan repositioning of influenza hemagglutinin stem facilitates the elicitation of protective cross-group antibody responses (2020, background): “In contrast, the immunologically subdominant stem region of HA is highly conserved among and across subtypes and targeted by a number of bNAbs capable of crossreacting with multiple viral subtypes [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] .”
- Quantifying B cells capable of producing broadly neutralizing antibodies against influenza serves as a metric to guide the development of a universal influenza vaccine (2016, unknown): “12 Cell 166, 1–15, July 28, 2016 Wu et al., 2015), clear evidence of their induction by vaccination had not been reported.”
- Structure and Function Analysis of an Antibody Recognizing All Influenza A Subtypes (2016, background): “…group 1 (Corti et al., 2010; Sui et al., 2009; Throsby et al., 2008;Wrammert et al., 2011), group 2 (Dunand et al., 2015; Ekiert et al., 2011; Friesen et al., 2014; Tan et al., 2014) and groups 1 and 2 viruses (Corti et al., 2011; Dreyfus et al., 2012; Na- kamura et al., 2013; Wu et al., 2015).”