Pharma Focus Asia

SARS-CoV-2 Neutralizing Antibodies Longevity, Breadth, and Evasion by Emerging Viral Variants

Fiona Tea, Alberto Ospina Stella, Anupriya Aggarwal, David Ross Darley, Deepti Pilli, Daniele Vitale, Vera Merheb, Fiona X. Z. Lee, Philip Cunningham, Gregory J. Walker, Christina Fichter, David A. Brown, William D. Rawlinson, Sonia R. Isaacs, Vennila Mathivanan, Markus Hoffmann, Stefan Pöhlman, Ohan Mazigi, Daniel Christ, Dominic E. Dwyer, Rebecca J. Rockett, Vitali Sintchenko, Veronica C. Hoad, David O. Irving, Gregory J. Dore, Iain B. Gosbell, Anthony D. Kelleher, Gail V. Matthews, Fabienne Brilot, Stuart G. Turville

Abstract
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibody neutralization response and its evasion by emerging viral variants and variant of concern (VOC) are unknown, but critical to understand reinfection risk and breakthrough infection following vaccination.

Introduction
Control of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic relies on population resistance to infection due to a postinfection and vaccination-induced immunity. Current questions relate to the level, breadth, and longevity of generated immunity and whether mutation of the virus will compromise immunity.

Methods:

Participants
This study investigated 2 cohorts of RT-PCR–confirmed convalescent individuals recruited from February to October 2020 in Australia (Table 1, Fig 1A). The Adapting to Pandemic Threats (ADAPT) cohort included 83 patients diagnosed at a community-based fever clinic whose sera was collected at 2 time points post-PCR positivity during the first wave (March to August, n = 166 samples).

Flow cytometry cell-based assay for detection of SARS-CoV-2 antibodies
A flow cytometry cell-based assay detected patient serum antibodies against SARS-CoV-2 antigens as for neuroimmunological autoantibodies.

Discussion:
The current study characterizes the breadth, longevity, and neutralizing capacity of SARS-CoV-2 antibody response in 2 Australian cohorts, encompassing a wide range of demographics and disease states, up to 7 months after COVID-19 diagnosis. We show the development of broad and sustained immunoreactivity against SARS-CoV-2 antigens and found high titers of Spike-binding and virus-neutralizing antibodies were associated with COVID-19 severity.

Acknowledgments:
We thank all the patients and donors who participated in this study. We thank Drs. Suat Dervish, Edwin Lau, and Maggie Wang for providing advice at the Flow Cytometry Core Facility of the Westmead Research Hub. We thank Ms. Rebecca Rielly, the Operation, and the Research Ethics and Governance teams at Kids Research for providing acces to the PC2 facility and advice on ethics and governance matters

Citation: Tea F, Ospina Stella A, Aggarwal A, Ross Darley D, Pilli D, Vitale D, et al. (2021) SARS-CoV-2 neutralizing antibodies: Longevity, breadth, and evasion by emerging viral variants. PLoS Med 18(7): e1003656. https://doi.org/10.1371/journal.pmed.1003656

Editor: Chiara Lazzeri, Azienda Ospedaliero Universitaria Careggi, ITALY

Received: February 5, 2021; Accepted: May 12, 2021; Published: July 6, 2021.

Copyright: © 2021 Tea et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: Data cannot be shared publicly because of ethical considerations. Data are available from St Vincent Hospital and Lifeblood Institutional Data Access / Ethics Committee (contact via FB) for researchers who meet the criteria for access to confidential data. Material transfer should be obtained through a Material Transfer Agreement.

Funding: This work was supported by Snow Medical (Australia, FB), The University of New South Wales Rapid Response grant (Australia, ADK), the University of Sydney Research Excellence Initiative grant (Australia, FB), the Medical Research Future Fund COVID-19 grant (MRFF2005760, SGT), Medical Research Future Fund Antiviral Development Call grant (DC), Medical Research Future Fund COVID-19 grant (MRFF2001684, ADK), the New South Wales Health COVID-19 Research Grants Round 2 (FB), and the Australian Governments for the provision of blood, blood products, and services for the Australian community (Australian Red Cross Lifeblood, IBG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: FB has received honoraria from Biogen Idec and Merck Serono as invited speaker. The other authors have declared that no competing interests exist.

Abbreviations:
ΔMFI, delta median fluorescence intensity; ADAPT, Adapting to Pandemic Threats; COVID-19, Coronavirus Disease 2019; GLM, general linear model; HSD, honestly significant difference; LIFE, Australian Red Cross Lifeblood cohort; NIBSC, National Institute for Biological Standards and Control; OE-PCR, overlap extension polymerase chain reaction; RBD, receptor-binding domain; RECOVERY, Randomized Evaluation of COVID-19 Therapy; RT-PCR, reverse transcription polymerase chain reaction; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2; VOC, variant of concern; WHO, World Health Organization.

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