Structure and Function Analysis of an Antibody Recognizing All Influenza A Subtypes

By N. Kallewaard, D. Corti, P. Collins, U. Neu, Josephine M. McAuliffe, Ebony Benjamin, Leslie Wachter-Rosati, F. Palmer-Hill, A. Q. Yuan, P. Walker and 19 more. 2016

386 citations recorded by the source corpus.

Summary Influenza virus remains a threat because of its ability to evade vaccine-induced immune responses due to antigenic drift. Here, we describe the isolation, evolution, and structure of a broad-spectrum human monoclonal antibody (mAb), MEDI8852, effectively reacting with all influenza A hemagglutinin (HA) subtypes. MEDI8852 uses the heavy-chain VH6-1 gene and has higher potency and breadth when compared to other anti-stem antibodies. MEDI8852 is effective in mice and ferrets with a therapeutic window superior to that of oseltamivir. Crystallographic analysis of Fab alone or in complex with H5 or H7 HA proteins reveals that MEDI8852 binds through a coordinated movement of CDRs to a highly conserved epitope encompassing a hydrophobic groove in the fusion domain and a large portion of the fusion peptide, distinguishing it from other structurally characterized cross-reactive antibodies. The unprecedented breadth and potency of neutralization by MEDI8852 support its development as immunotherapy for influenza virus-infected humans.

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

1. Barney S. Graham
2. D. Veesler
3. M. Kanekiyo

In Radiology, Nuclear Medicine and Imaging

1. Neil P. King
2. M. Kanekiyo
3. Daniel Ellis
4. David Baker
5. Barney S. Graham
6. Frances H. Arnold

Citations in the corpus

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• Design of Nanoparticulate Group 2 Influenza Virus Hemagglutinin Stem Antigens That Activate Unmutated Ancestor B Cell Receptors of Broadly Neutralizing Antibody Lineages (2018, positive): “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).”
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• 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] .”