ArticleVaccine2019
Structural and antigenic characterization of a computationally-optimized H5 hemagglutinin influenza vaccine.
Article in Vaccine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Mapping hemagglutinin residues driving antigenic diversity in H5Nx avian influenza viruses.Journal of virology · 2026Article
- H3 hemagglutinin proteins optimized for 2018 to 2022 elicit neutralizing antibodies across panels of modern influenza A(H3N2) viruses.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- H9 Consensus Hemagglutinin Subunit Vaccine with Adjuvants Induces Robust Mucosal and Systemic Immune Responses in Mice by Intranasal Administration.Microorganisms · 2024Article
- Structural basis for the broad antigenicity of the computationally optimized influenza hemagglutinin X6.Structure (London, England : 1993) · 2024Article
- Influenza virus immune imprinting dictates the clinical outcomes in ferrets challenged with highly pathogenic avian influenza virus H5N1.Frontiers in veterinary science · 2023Article
- Differential Recognition of Computationally Optimized H3 Hemagglutinin Influenza Vaccine Candidates by Human Antibodies.Journal of virology · 2022Article
- The Pre-Existing Human Antibody Repertoire to Computationally Optimized Influenza H1 Hemagglutinin Vaccines.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Protein engineering strategies for rational immunogen design.NPJ vaccines · 2021Review
- Next-Generation Computationally Designed Influenza Hemagglutinin Vaccines Protect against H5Nx Virus Infections.Pathogens (Basel, Switzerland) · 2021Article
- Next-Generation Influenza HA Immunogens and Adjuvants in Pursuit of a Broadly Protective Vaccine.Viruses · 2021Review
- Review
- Computationally Optimized Broadly Reactive H2 HA Influenza Vaccines Elicited Broadly Cross-Reactive Antibodies and Protected Mice from Viral Challenges.Journal of virology · 2020Article
- High-Yield Expression and Purification of Recombinant Influenza Virus Proteins from Stably-Transfected Mammalian Cell Lines.Vaccines · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Influenza A virus is a leading cause of death worldwide. Viruses of the H5 subtype have the potential to induce high mortality, and no vaccines are currently available to protect against H5 influenza viruses in the event of an outbreak. Experimental vaccination with one clade 2 virus does not protect against other subclades. The computationally optimized broadly reactive (COBRA) methodology was previously used to generate a H5 hemagglutinin (HA) antigen (COBRA2) that elicited increased serological breadth against multiple clade 2 H5N1 influenza viruses. In this report, we structurally and antigenically characterized the COBRA2 HA antigen. We examined the biochemical characteristics of the COBRA2 protein and determined the protein is correctly cleaved, properly folded into a trimeric structure, and antigenically correct by probing with HA head- and stem-specific monoclonal antibodies (mAbs). We further probed the antigenicity by examining binding of a panel of H5 mouse mAbs to the COBRA2 antigen, as well as several other HA antigens. We determined the X-ray crystal structure of the COBRA2 HA antigen to 2.8 Å and the protein was observed to be in the expected trimeric form. The COBRA2 HA was structurally similar to the naturally occurring H5 HA antigens and suggests the protein folds similar to known HA structures. Overall, our data allow us to formulate a hypothesis on the mechanism of increased breadth due to vaccination with the COBRA2 HA antigen, which is that the protein incorporates antigenic sites from numerous HA antigens, and elicits mAbs with limited breadth, but with diversity in targeted antigenic sites.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.