Development and Assessment of a Pooled Serum as Candidate Standard to Measure Influenza A Virus Group 1 Hemagglutinin Stalk-Reactive Antibodies.

Autor: Carreño JM; Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA., McDonald JU; Division of Virology, National Institute for Biological Standards and Control (NIBSC), South Mimms, Potters Bar EN6 3QG, UK., Hurst T; Division of Virology, National Institute for Biological Standards and Control (NIBSC), South Mimms, Potters Bar EN6 3QG, UK., Rigsby P; Division of Analytical and Biological Sciences, National Institute for Biological Standards and Control (NIBSC), South Mimms, Potters Bar EN6 3QG, UK., Atkinson E; Division of Analytical and Biological Sciences, National Institute for Biological Standards and Control (NIBSC), South Mimms, Potters Bar EN6 3QG, UK., Charles L; Division of Virology, National Institute for Biological Standards and Control (NIBSC), South Mimms, Potters Bar EN6 3QG, UK., Nachbagauer R; Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA., Behzadi MA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA., Strohmeier S; Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA.; Department of Biotechnology, University of Natural Resources and Life Sciences, 1190 Vienna, Austria., Coughlan L; Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA., Aydillo T; Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA.; Global Health and Emerging Pathogens Institute, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA., Brandenburg B; Janssen Vaccines & Prevention BV, 2333 CP Leiden, The Netherlands., García-Sastre A; Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA.; Global Health and Emerging Pathogens Institute, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA.; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA.; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA., Kaszas K; Janssen Vaccines & Prevention BV, 2333 CP Leiden, The Netherlands., Levine MZ; Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA., Manenti A; VisMederi Research srl, 53100 Siena, Italy., McDermott AB; Vaccine Immunology Program (VIP), Vaccine Research Center (VRC), National Institutes of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA., Montomoli E; Department of Molecular and Developmental Medicine, University of Siena, 53100 Siena, Italy., Muchene L; Janssen Vaccines & Prevention BV, 2333 CP Leiden, The Netherlands., Narpala SR; Vaccine Immunology Program (VIP), Vaccine Research Center (VRC), National Institutes of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA., Perera RAPM; School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China., Salisch NC; Janssen Vaccines & Prevention BV, 2333 CP Leiden, The Netherlands., Valkenburg SA; School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China., Zhou F; Influenza Center, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway.; K.G. Jebsen Center for influenza vaccines, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway., Engelhardt OG; Division of Virology, National Institute for Biological Standards and Control (NIBSC), South Mimms, Potters Bar EN6 3QG, UK., Krammer F; Department of Microbiology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA.
Jazyk: angličtina
Zdroj: Vaccines [Vaccines (Basel)] 2020 Nov 09; Vol. 8 (4). Date of Electronic Publication: 2020 Nov 09.
DOI: 10.3390/vaccines8040666
Abstrakt: The stalk domain of the hemagglutinin has been identified as a target for induction of protective antibody responses due to its high degree of conservation among numerous influenza subtypes and strains. However, current assays to measure stalk-based immunity are not standardized. Hence, harmonization of assay readouts would help to compare experiments conducted in different laboratories and increase confidence in results. Here, serum samples from healthy individuals ( n = 110) were screened using a chimeric cH6/1 hemagglutinin enzyme-linked immunosorbent assay (ELISA) that measures stalk-reactive antibodies. We identified samples with moderate to high IgG anti-stalk antibody levels. Likewise, screening of the samples using the mini-hemagglutinin (HA) headless construct #4900 and analysis of the correlation between the two assays confirmed the presence and specificity of anti-stalk antibodies. Additionally, samples were characterized by a cH6/1N5 virus-based neutralization assay, an antibody-dependent cell-mediated cytotoxicity (ADCC) assay, and competition ELISAs, using the stalk-reactive monoclonal antibodies KB2 (mouse) and CR9114 (human). A "pooled serum" (PS) consisting of a mixture of selected serum samples was generated. The PS exhibited high levels of stalk-reactive antibodies, had a cH6/1N5-based neutralization titer of 320, and contained high levels of stalk-specific antibodies with ADCC activity. The PS, along with blinded samples of varying anti-stalk antibody titers, was distributed to multiple collaborators worldwide in a pilot collaborative study. The samples were subjected to different assays available in the different laboratories, to measure either binding or functional properties of the stalk-reactive antibodies contained in the serum. Results from binding and neutralization assays were analyzed to determine whether use of the PS as a standard could lead to better agreement between laboratories. The work presented here points the way towards the development of a serum standard for antibodies to the HA stalk domain of phylogenetic group 1.
Databáze: MEDLINE