Structural and Functional Bases for Broad-Spectrum Neutralization of Avian and Human Influenza A Viruses

By J. Sui, W. C. Hwang, S. Pérez, G. Wei, Daniel Aird, Li-mei Chen, E. Santelli, B. Stec, G. Cadwell, M. Ali and 9 more. Nature Structural &Molecular Biology, 2009

1,190 citations recorded by the source corpus.

Influenza virus remains a serious health threat, owing to its ability to evade immune surveillance through rapid genetic drift and reassortment. Here we used a human non-immune antibody phage-display library and the H5 hemagglutinin ectodomain to select ten neutralizing antibodies (nAbs) that were effective against all group 1 influenza viruses tested, including H5N1 'bird flu' and the H1N1 'Spanish flu'. The crystal structure of one such nAb bound to H5 shows that it blocks infection by inserting its heavy chain into a conserved pocket in the stem region, thus preventing membrane fusion. Nine of the nAbs employ the germline gene VH1-69, and all seem to use the same neutralizing mechanism. Our data further suggest that this region is recalcitrant to neutralization escape and that nAb-based immunotherapy is a promising strategy for broad-spectrum protection against seasonal and pandemic influenza viruses.

Subfields: Epidemiology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/a0ed0d8eecbfe77dad7e8c46acba3e9524422d66

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Citations in the corpus

Beyond natural antibodies: the power of in vitro display technologies (2011, background): “Antibodies also have great potential in blocking protein interactions associated with viral entry into target cells, illustrated by antibodies selected from naive antibody libraries against recombinant hemagglutinin 5 (H5) influenza ectodomai”
Potent Protection against H5N1 and H7N9 Influenza via Childhood Hemagglutinin Imprinting (2016, background): “Given the immunodominant nature of HA head reactivities (13,14,26,28), conserved HA head epitopes shared within, but not between, HA groups (29) may play a role in these patterns of protection.”
Design of an HA2-based Escherichia coli expressed influenza immunogen that protects mice from pathogenic challenge (2010, background): “Broadly neutralizing HA2 stem-specific monoclonal antibodies with neutralizing activity for H1 clade viruses (14, 15) and recently for H3 subtype viruses (31) have been isolated.”
Hemagglutinin-Pseudotyped Green Fluorescent Protein-Expressing Influenza Viruses for the Detection of Influenza Virus Neutralizing Antibodies (2009, background): “A few HA-specific MAbs with broad cross-neutralization activities have recently been described (5, 18, 20), and the use of HA-pseudotyped GFP-expressing influenza viruses should make possible rapid screenings for the identification of additional antibodies with such broad cross-neutralizing activiti”
Next-Generation Influenza Vaccines. (2020, background): “…breadth against multiple subtype viruses within influenza A group 1 subtypes (Okuno et al. 1993; Throsby et al. 2008; Ekiert et al. 2009; Sui et al. 2009), group 2 subtypes (Ekiert et al. 2011; Friesen et al. 2014), or across both group 1 and group 2 subtypes (Corti et al. 2011;…”