Comparative Analysis of SARS-CoV-2 Antigenicity across Assays and in Human and Animal Model Sera

• Type of Material: Article
• Authors: Barbara Mühlemann, Freie Universität Berlin; Samuel H. Wilks, University of Cambridge; Lauren Baracco, University of Maryland, Baltimore; Meriem Bekliz, University of Geneva; Juan Manuel Carreño, Icahn School fo Medicine at Mount Sinai; Victor M. Corman, Freie Universität Berlin; Meredith E. Davis-Gardner, Emory University; Wanwisa Dejnirattisai, University of Oxford; Michael S. Diamond, Washington University, St. Louis; Daniel C. Douek, National Institutes of Health; Christian Drosten, Freie Universität Berlin; Isabella Exkerle, University of Geneva; Venkata Viswanadh EDARA, Emory University; Madison Leigh Ellis, Emory University; Ron A.M. Fouchier, Erasmus Medical Center; Matthew Frieman, University of Maryland, Baltimore; Sucheta Godbole, National Institutes of Health; Bart Haagmans, Erasmus Medical Center; Peter J. Halfmann, University of Wisconsin, Madison; Amy R. Henry, National Institutes of Health; Terry C. Jones, Freie Universität Berlin; Leach C. Katzelnick, National Institutes of Health; Yoshihiro Kawaoka, University of Wisconsin, Madison; Janine Kimpel, Medical University of Innsbruck; Florian Krammer, Icahn School of Medicine at Mount Sinai; Lilin Lai, Emory University; Chang Liu, University of Oxford; Sabrina Lusvarghi, U.S. Food and Drug Administration; Benjamin Meyer, University of Geneva; Juthathip Mongkolsapaya, University of Oxford; David C. Montefiori, Duke University; Anna Mykytyn, Erasmus Medical Center; Antonia Netzl, University of Cambridge; Simon Pollett, Uniformed Services University of the Health Sciences; Annika Rössler, Medical University of Innsbruck; Gavin R. Screaton, University of Oxford; Xiaoying Shen, Duke University; Alex Sigal, University of KwaZulu, Natal; Viviana Simon, Icahn School of Medicine at Mount Sinai; Rahul Subramanian, National Institutes of Health; Piyada Supasa, University of Oxford; Mehul Suthar, Emory University; Sina Türeli, University of Cambridge; Wei Wang, U.S. Food and Drug Administration; Carol D. Weiss, U.S. Food and Drug Administration; Derek J. Smith, University of Cambridge
• Language: English
• Date: 2023-09-27
• Publisher: NIH
• Publication Version: Preprint (Prior to Peer Review)
• Copyright Statement: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): https://doi.org/10.1101/2023.09.27.559689
• Title of Journal or Parent Work: bioRxiv
• Start Page: 559689
• Grant/Funding Information: YK: Acknowledges support from a Research Program on Emerging and Reemerging Infectious Diseases (JP21fk0108552 and JP21fk0108615), a Project Promoting Support for Drug Discovery (JP21nf0101632), the Japan Program for Infectious Diseases Research and Infrastructure (JP22wm0125002), and the University of Tokyo Pandemic Preparedness, Infection and Advanced Research Center (UTOPIA) grant (JP223fa627001) from the Japan Agency for Medical Research and Development.; SHW, ST, AN, TCJ, DJS: supported by the NIH NIAID Centers of Excellence for Influenza Research and Response (CEIRR) contract 75N93021C00014 as part of the SAVE program.; MSD: National Institutes of Health R01 AI157155 and NIAID Centers of Excellence for Influenza Research and Response (CEIRR) contracts 75N93021C00014 and 75N93019C00051.; K: NIH NIAID Centers of Excellence for Influenza Research and Response (CEIRR) contract 75N93021C00014 as part of the SAVE program, European Union’s Horizon 2020 research and innovation program under grant agreement No. 101016174, and the Austrian Science Fund (FWF) with the project number P35159-B.; LCK: Supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases.; VMC: Participant in the BIH-Charité Clinician Scientist Program funded by Charité - Universitätsmedizin Berlin and the Berlin Institute of Health.; CD: ECDC project Aurorae (NP/21/2021/DPR/25121) and EU Hera project Durable (101102733).; RS: Appointment to the NIAID Emerging Leaders in Data Science Research Participation Program. The Emerging Leaders in Data Science Research Participation Program is administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy (DOE) and NIAID. ORISE is managed by Oak Ridge Associated Universities (ORAU) under DOE contract number DE-SC0014664.; MS, VVE, MD-G, LL, ME, DCD: Supported in part by grants (NIH P51OD011132, 3U19AI057266-17S1, HHSN272201400004C, NIH/NIAID CEIRR under contract 75N93021C00017 to Emory University) from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Emory Executive Vice President for Health Affairs Synergy Fund award, the Pediatric Research Alliance Center for Childhood Infections and Vaccines and Children’s Healthcare of Atlanta, COVID-Catalyst-I3 Funds from the Woodruff Health Sciences Center and Emory School of Medicine, Woodruff Health Sciences Center 2020 COVID-19 CURE Award. Funders played no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.; BM, VMC, CD, TCJ: Funded by German Federal Ministry of Education and Research through project DZIF (8040701710 and 8064701703) and VARIpath (01KI2021), and the German Federal Ministry of Health through project SeroVarCoV.; GRS: The Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS), China (2018-I2M-2-002), Schmidt Futures, and Red Avenue Foundation. The Wellcome Centre for Human Genetics is supported by the Wellcome Trust (090532/Z/09/Z).; DCD, ARH, SG: Funded in part by the intramural program of the National Institutes of Health. AS: The cohort was supported by the Bill and Melinda Gates Foundation award INV-018944 (to A.S.). SP: Was supported by awards from the Defense Health Program (HU00012020067) and the National Institute of Allergy and Infectious Disease (HU00011920111). The EPICC protocol was executed by the Infectious Disease Clinical Research Program (IDCRP), a Department of Defense (DoD) program executed by the Uniformed Services University of the Health Sciences (USUHS) through a cooperative agreement by the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF).; AN was supported by the Gates Cambridge Trust.
• Keywords: neutralization assays; newly arising variants; SARS-CoV-2
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Immunology; Biology, Virology

Abstract

The antigenic evolution of SARS-CoV-2 requires ongoing monitoring to judge the immune escape of newly arising variants. A surveillance system necessitates an understanding of differences in neutralization titers measured in different assays and using human and animal sera. We compared 18 datasets generated using human, hamster, and mouse sera, and six different neutralization assays. Titer magnitude was lowest in human, intermediate in hamster, and highest in mouse sera. Fold change, immunodominance patterns and antigenic maps were similar among sera. Most assays yielded similar results, except for differences in fold change in cytopathic effect assays. Not enough data was available for conclusively judging mouse sera, but hamster sera were a consistent surrogate for human first-infection sera.