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Author Notes:

Larry J. Anderson, larry.anderson@emory.edu

X.C., C.A.R., L.J.A. and E.J.A. proposed and designed the experiments. X.C., H-Y.S. and C.Y.L. performed ADCC experiments. X.C. and H-Y.S performed anti-influenza HA IgG ELISA, Western Blot, Flowcytometry and neuraminidase activity assay. J.T. performed HA-mediated membrane fusion assay. J.R.W. and S.G. generated monoclonal antibody E4.

This study was funded by Center of Excellence for Influenza Research and Surveillance (CEIRS) to L.J.A. We would like to thank Rebecca Kondor at CDC for providing us influenza strain information. We thank staff at UGA for kindly providing 2014-15 vaccinated specimens. Finally, we would like to thank all the participating volunteers for donating their specimens.

LJA has done paid consultancies on RSV vaccines for Bavarian Nordic, ClearPath Vaccines Company, Pfizer, and ADVI; his laboratory is currently receiving funding through Emory University from Pfizer for laboratory studies for RSV surveillance studies in adults, and Sciogen for animal studies of RSV vaccines; he is a co-inventor on several CDC patents on the RSV G protein and its CX3C chemokine motif relative to immune therapy and vaccine development; and is co-inventor on a patent filing for use of RSV platform VLPs with the F and G proteins for vaccines.

E.J.A has consulted for Pfizer, Sanofi Pasteur, Janssen, and Medscape, and his institution receives funds to conduct clinical research unrelated to this manuscript from MedImmune, Regeneron, PaxVax, Pfizer, GSK, Merck, Sanofi-Pasteur, Janssen, and Micron. He also serves on a safety monitoring board for Kentucky BioProcessing, Inc. and Sanofi Pasteur. His institution has also received funding from NIH to conduct clinical trials of Moderna and Janssen COVID-19 vaccines.

Subjects:

Research Funding:

This study was funded through HHSN272201400004C (NIAID Centers of Excellence for Influenza Research and Surveillance, CEIRS)

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention or funding agency.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Virology
  • Antibody-dependent cellular cytotoxicity
  • (ADCC)
  • Influenza hemagglutinin (HA)
  • Influenza neuraminidase (NA)
  • Influenza virus vaccine
  • UNITED-STATES
  • A VIRUS
  • NEURAMINIDASE ANTIBODY
  • ACTIVE-SITE
  • HEMAGGLUTININ
  • SEASON
  • IMMUNIZATION
  • IMMUNITY

Functional antibody-dependent cell mediated cytotoxicity (ADCC) responses to vaccine and circulating influenza strains following vaccination

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Journal Title:

VIROLOGY

Volume:

Volume 569

Publisher:

, Pages 44-55

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Novel cell-based assays were developed to assess antibody-dependence cellular cytotoxicity (ADCC) antibodies against both vaccine and a representative circulation strain HA and NA proteins for the 2014-15 influenza season. The four assays using target cells stably expressing one of the four proteins worked well. In pre- and post-vaccine sera from 70 participants in a pre-season vaccine trial, we found ADCC antibodies and a rise in ADCC antibody titer against target cells expressing the 4 proteins but a much higher titer for the vaccine than the circulating HA in both pre-and post-vaccine sera. These differences in HA ADCC antibodies were not reflected in differences in HA binding antibodies. Our observations suggested that relatively minor changes on the subtype HA can result in large differences in ADCC activity.

Copyright information:

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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