Broadly neutralizing influenza hemagglutinin stem-specific antibody CR8020 targets residues that are prone to escape due to host selection pressure
| Autor: | Viswanathan Sasisekharan, Ram Sasisekharan, Kannan Tharakaraman, David Cain, Vidya Subramanian |
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| Přispěvatelé: | Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. School of Engineering, MIT Skoltech Initiative, Koch Institute for Integrative Cancer Research at MIT, Tharakaraman, Kannan, Subramanian, Vidya, Cain, David, Sasisekharan, Viswanathan, Sasisekharan, Ram |
| Rok vydání: | 2014 |
| Předmět: |
Models
Molecular Cancer Research Amino Acid Motifs Hemagglutinin (influenza) Hemagglutinin Glycoproteins Influenza Virus medicine.disease_cause Antibodies Viral Influenza A Virus H7N9 Subtype Microbiology Epitope Antigenic drift Article Neutralization Tests Virology Immunology and Microbiology(all) Influenza Human Influenza A virus medicine Humans Molecular Biology Immune Evasion biology Influenza A Virus H3N2 Subtype Antibodies Monoclonal Fragment crystallizable region Antibodies Neutralizing Immune complex 3. Good health Epitope mapping Host-Pathogen Interactions biology.protein Parasitology Antibody Epitope Mapping |
| Zdroj: | PMC |
| ISSN: | 1934-6069 |
| Popis: | Broadly neutralizing antibodies (bNAb) that target a conserved region of a viral antigen hold significant therapeutic promise. CR8020 is a bNAb that targets the stem region of influenza A virus (IAV) hemagglutinin (HA). CR8020 is currently being evaluated for prophylactic use against group 2 IAVs in phase II studies. Structural and computational analyses reported here indicate that CR8020 targets HA residues that are prone to antigenic drift and host selection pressure. Critically, CR8020 escape mutation is seen in certain H7N9 viruses from recent outbreaks. Furthermore, the ability of the bNAb Fc region to effectively engage activating Fcγ receptors (FCγR) is essential for antibody efficacy. In this regard, our data indicate that the membrane could sterically hinder the formation of HA-CR8020-FcγRIIa/HA-IgG-FcγRIIIa ternary complexes. Altogether, our analyses suggest that epitope mutability and accessibility to immune complex assembly are important attributes to consider when evaluating bNAb candidates for clinical development. National Institutes of Health (U.S.) (Merit Award R37 GM057073-13) Singapore. National Research Foundation (Singapore-MIT Alliance for Research and Technology) |
| Databáze: | OpenAIRE |
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