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Activity of human serum antibodies in an influenza virus hemagglutinin stalk-based ADCC reporter assay correlates with activity in a CD107a degranulation assay.
Chromikova, Veronika; Tan, Jessica; Aslam, Sadaf; Rajabhathor, Arvind; Bermudez-Gonzalez, Maria; Ayllon, Juan; Simon, Viviana; García-Sastre, Adolfo; Salaun, Bruno; Nachbagauer, Raffael; Krammer, Florian.
Afiliación
  • Chromikova V; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Tan J; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Graduate School of Biological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Aslam S; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Rajabhathor A; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Bermudez-Gonzalez M; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Ayllon J; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Simon V; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • García-Sastre A; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New Yo
  • Salaun B; GlaxoSmithKline, Rixensart, Belgium.
  • Nachbagauer R; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Krammer F; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: florian.krammer@mssm.edu.
Vaccine ; 38(8): 1953-1961, 2020 02 18.
Article en En | MEDLINE | ID: mdl-31959425
The stalk of the influenza virus hemagglutinin (HA) is an attractive target for antibody-based universal influenza virus vaccine development. While antibodies that target this part of the virus can be neutralizing, it has been shown in recent years that Fc receptor-mediated effector functions are of significant importance for the protective effect of anti-stalk antibodies. Several assays to measure Fc-Fc receptor interaction-based effector functions like antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis exist, but they suffer from limitations such as low throughput and high run-to-run variability. Reporter assays for antibody-dependent cellular cytotoxicity based on reporter cells that express luciferase upon engagement of human FcγRIIIa with the Fc of antigen-bound antibodies have been developed as well. These reporter assays can be used in a higher throughput setting with limited run-to-run assay variability but since they express only one Fc receptor, their biological relevance is unclear. Here we optimized an antibody-dependent cellular cytotoxicity reporter assay to measure the activity of antibodies to the conserved stalk domain of H1 hemagglutinin. The assay was then correlated to a CD107a-based degranulation assay, and a strong and significant correlation could be observed. This data suggests that the FcγRIIIa-based reporter assay is a good substitute for functional assays, especially in settings where larger sample numbers need to be analyzed.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glicoproteínas Hemaglutininas del Virus de la Influenza / Gripe Humana / Anticuerpos Antivirales Límite: Adolescent / Adult / Aged / Child, preschool / Humans / Infant / Middle aged Idioma: En Revista: Vaccine Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Glicoproteínas Hemaglutininas del Virus de la Influenza / Gripe Humana / Anticuerpos Antivirales Límite: Adolescent / Adult / Aged / Child, preschool / Humans / Infant / Middle aged Idioma: En Revista: Vaccine Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos