Human antibody 3E1 targets the HA stem region of H1N1 and H5N6 influenza A viruses

Wang, Wenshuai; Sun, Xiaoyu; Li, Yanbing; Su, Jie; Ling, Zhiyang; Zhang, Tianlong; Wang, Fang; Zhou, Hong; Chen, Hualan; Ding, Jianping; Sun, Bing

doi:10.1038/ncomms13577

Cited by 32 publications

(30 citation statements)

References 51 publications

(97 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They are present at much lower levels than HA head antibodies but anti-stalk mAbs can be cloned from human subjects (Wang et al, 2016). To determine reactivity to the stalk region of HA, IVIg and fragments of IVIg were reacted with a recombinant H5 protein (A/Vietnam1203/04) in a solid phase enzyme linked assay.…”

Section: Resultsmentioning

confidence: 99%

Intravenous Immunoglobulin Protects Against Severe Pandemic Influenza Infection

Rockman

Lowther

Camuglia³

et al. 2017

EBioMedicine

View full text Add to dashboard Cite

Influenza is a highly contagious, acute, febrile respiratory infection that can have fatal consequences particularly in individuals with chronic illnesses. Sporadic reports suggest that intravenous immunoglobulin (IVIg) may be efficacious in the influenza setting. We investigated the potential of human IVIg to ameliorate influenza infection in ferrets exposed to either the pandemic H1N1/09 virus (pH1N1) or highly pathogenic avian influenza (H5N1). IVIg administered at the time of influenza virus exposure led to a significant reduction in lung viral load following pH1N1 challenge. In the lethal H5N1 model, the majority of animals given IVIg survived challenge in a dose dependent manner. Protection was also afforded by purified F(ab′)2 but not Fc fragments derived from IVIg, supporting a specific antibody-mediated mechanism of protection. We conclude that pre-pandemic IVIg can modulate serious influenza infection-associated mortality and morbidity. IVIg could be useful prophylactically in the event of a pandemic to protect vulnerable population groups and in the critical care setting as a first stage intervention.

show abstract

Section: Resultsmentioning

confidence: 99%

Intravenous Immunoglobulin Protects Against Severe Pandemic Influenza Infection

Rockman

Lowther

Camuglia³

et al. 2017

EBioMedicine

View full text Add to dashboard Cite

show abstract

“…The DNA sequences of four of the bnAbs 1F2, 1F4, 1E1, and 1G1 revealed V H 3–23 and V L 3–15 gene usage, whereas two the bnAbs corresponded to V H 3–30/V L 3–20 (1C4) and V H 1–69/V L 3–20 (3C4) usage [ 69 ]. The DNA sequence of 3E1 indicated its germ line usage of IGHV4-4x07 and IGKV1-5x03 genes with less somatic hypermutation [ 71 ].…”

Section: Stem-directed Bnabsmentioning

confidence: 99%

“…At the lower region of the epitope, the HCDR2 loop interacts with the C-terminus of the outermost β-strand preceding helix A. The distinct conformational epitope of 3E1 combines the major regions of the epitopes recognized by both group 1 HA sbnAbs (CR6261, FI6v3, CR9114, F10, Fab3.1 and C179) and group 2 HA sbnAbs (CR8020, CR8043) [ 71 ]. Similar to group 1 sbnAbs, 3E1 makes extensive hydrophobic contacts with residues of the F subdomain via large hydrophobic and aromatic residues, and similar to group 2 sbnAbs, 3E1 contacts residues of the fusion peptide and the outermost β-strand.…”

Section: Stem-directed Bnabsmentioning

confidence: 99%

Neutralizing Antibodies Targeting the Conserved Stem Region of Influenza Hemagglutinin

2020

View full text Add to dashboard Cite

Influenza continues to be a public health threat despite the availability of annual vaccines. While vaccines are generally effective at inducing strain-specific immunity, they are sub-optimal or ineffective when drifted or novel pandemic strains arise due to sequence changes in the major surface glycoprotein hemagglutinin (HA). The discovery of a large number of antibodies targeting the highly conserved stem region of HAs that are capable of potently neutralizing a broad range of virus strains and subtypes suggests new ways to protect against influenza. The structural characterization of HA stem epitopes and broadly neutralizing antibody paratopes has enabled the design of novel proteins, mini-proteins, and peptides targeting the HA stem, thus providing a foundation for the design of new vaccines. In this narrative, we comprehensively review the current knowledge about stem-directed broadly neutralizing antibodies and the structural features contributing to virus neutralization.

show abstract

“…F10 binds to a highly conserved pocket in the HA stem region and shows remarkable cross-subtype binding and neutralizing potency against influenza virus H1, H2, H5, H6, H8 and H9 subtypes [ 96 ]. Recently, several anti-stem antibodies have been reported response to group 1 subtypes, such as Mab3.1, 3E1 and FISW84 [ 11 , 108 , 121 ]. Interestingly, the monoclonal antibody FISW84 could bind to H1 influenza viruses and its interaction near the junction between the ectodomain and the membrane anchor [ 11 ].…”

Section: Bnabs Specific For the Ha2 Stem Regionmentioning

confidence: 99%

Structural Insights for Anti-Influenza Vaccine Design

Han

Chen

Han

et al. 2019

Computational and Structural Biotechnology Journal

View full text Add to dashboard Cite

Influenza A virus are a persistent and significant threat to human health, and current vaccines do not provide sufficient protection due to antigenic drift, which allows influenza viruses to easily escape immune surveillance and antiviral drug activity. Influenza hemagglutinin (HA) is a glycoprotein needed for the entry of enveloped influenza viruses into host cells and is a potential target for anti-influenza humoral immune responses. In recent years, a number of broadly neutralizing antibodies (bnAbs) have been isolated, and their relative structural information obtained from the crystallization of influenza antigens in complex with bnAbs has provided some new insights into future influenza vaccine research. Here, we review the current knowledge of the HA-targeted bnAbs and the structure-based mechanisms contributing to neutralization. We also discuss the potential for this structure-based approach to overcome the challenge of obtaining a highly desired “universal” influenza vaccine, especially on small proteins and peptides.

show abstract

Human antibody 3E1 targets the HA stem region of H1N1 and H5N6 influenza A viruses

Cited by 32 publications

References 51 publications

Intravenous Immunoglobulin Protects Against Severe Pandemic Influenza Infection

Intravenous Immunoglobulin Protects Against Severe Pandemic Influenza Infection

Neutralizing Antibodies Targeting the Conserved Stem Region of Influenza Hemagglutinin

Structural Insights for Anti-Influenza Vaccine Design

Contact Info

Product

Resources

About