Emergence and antibody evasion of BQ, BA.2.75 and SARS-CoV-2 recombinant sub-lineages in the face of maturing antibody breadth at the population levelResearch in context
Anouschka Akerman,
Vanessa Milogiannakis,
Tyra Jean,
Camille Esneau,
Mariana Ruiz Silva,
Timothy Ison,
Christina Fichter,
Joseph A. Lopez,
Deborah Chandra,
Zin Naing,
Joanna Caguicla,
Daiyang Li,
Gregory Walker,
Supavadee Amatayakul-Chantler,
Nathan Roth,
Sandro Manni,
Thomas Hauser,
Thomas Barnes,
Anna Condylios,
Malinna Yeang,
Maureen Wong,
Charles S.P. Foster,
Kenta Sato,
Sharon Lee,
Yang Song,
Lijun Mao,
Allison Sigmund,
Amy Phu,
Ann Marie Vande More,
Stephanie Hunt,
Mark Douglas,
Ian Caterson,
Warwick Britton,
Kerrie Sandgren,
Rowena Bull,
Andrew Lloyd,
Jamie Triccas,
Stuart Tangye,
Nathan W. Bartlett,
David Darley,
Gail Matthews,
Damien J. Stark,
Kathy Petoumenos,
William D. Rawlinson,
Ben Murrell,
Fabienne Brilot,
Anthony L. Cunningham,
Anthony D. Kelleher,
Anupriya Aggarwal,
Stuart G. Turville
Affiliations
Anouschka Akerman
The Kirby Institute, University of New South Wales, New South Wales, Australia
Vanessa Milogiannakis
The Kirby Institute, University of New South Wales, New South Wales, Australia
Tyra Jean
Serology and Virology Division (SAViD), NSW Health Pathology, Randwick, Australia
Camille Esneau
Hunter Medical Research Institute, University of Newcastle, Callaghan, Australia
Mariana Ruiz Silva
The Kirby Institute, University of New South Wales, New South Wales, Australia
Timothy Ison
The Kirby Institute, University of New South Wales, New South Wales, Australia
Christina Fichter
The Kirby Institute, University of New South Wales, New South Wales, Australia
Joseph A. Lopez
Brain Autoimmunity Group, Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, School of Medical Sciences, New South Wales, Australia
Deborah Chandra
The Kirby Institute, University of New South Wales, New South Wales, Australia
Zin Naing
Serology and Virology Division (SAViD), NSW Health Pathology, Randwick, Australia
Joanna Caguicla
Serology and Virology Division (SAViD), NSW Health Pathology, Randwick, Australia
Daiyang Li
Serology and Virology Division (SAViD), NSW Health Pathology, Randwick, Australia
Gregory Walker
Serology and Virology Division (SAViD), NSW Health Pathology, Randwick, Australia
Supavadee Amatayakul-Chantler
Department of Bioanalytical Sciences, Plasma Product Development, Research & Development, CSL Behring, Australia
Nathan Roth
Department of Bioanalytical Sciences, Plasma Product Development, Research & Development, CSL Behring AG, Bern, Switzerland
Sandro Manni
Plasma Product Development, Research & Development, CSL Behring AG, Bern, Switzerland
Thomas Hauser
Plasma Product Development, Research & Development, CSL Behring AG, Bern, Switzerland
Thomas Barnes
Plasma Product Development, Research & Development, CSL Behring AG, Bern, Switzerland
Anna Condylios
Serology and Virology Division (SAViD), NSW Health Pathology, Randwick, Australia
Malinna Yeang
Serology and Virology Division (SAViD), NSW Health Pathology, Randwick, Australia
Maureen Wong
Serology and Virology Division (SAViD), NSW Health Pathology, Randwick, Australia
Charles S.P. Foster
Serology and Virology Division (SAViD), NSW Health Pathology, Randwick, Australia
Kenta Sato
Molecular Diagnostic Medicine Laboratory, Sydpath, St Vincent's Hospital, Sydney, New South Wales, Australia
Sharon Lee
Research & Education Network, Westmead Hospital, WSLHD, New South Wales, Australia
Yang Song
Research & Education Network, Westmead Hospital, WSLHD, New South Wales, Australia
Lijun Mao
Research & Education Network, Westmead Hospital, WSLHD, New South Wales, Australia
Allison Sigmund
Research & Education Network, Westmead Hospital, WSLHD, New South Wales, Australia
Amy Phu
Research & Education Network, Westmead Hospital, WSLHD, New South Wales, Australia
Ann Marie Vande More
Royal Prince Alfred Hospital, SLHD, New South Wales, Australia
Stephanie Hunt
Royal Prince Alfred Hospital, SLHD, New South Wales, Australia
Mark Douglas
The Westmead Institute for Medical Research, Westmead, New South Wales, Australia; Centre for Infectious Diseases and Microbiology, Sydney Institute for Infectious Diseases, The University of Sydney at Westmead Hospital, Westmead, NSW, Australia
Ian Caterson
Royal Prince Alfred Hospital, SLHD, New South Wales, Australia
Warwick Britton
The Centenary Institute, University of Sydney, Camperdown, New South Wales 2050, Australia
Kerrie Sandgren
The Westmead Institute for Medical Research, Westmead, New South Wales, Australia
Rowena Bull
The Kirby Institute, University of New South Wales, New South Wales, Australia
Andrew Lloyd
The Kirby Institute, University of New South Wales, New South Wales, Australia
Jamie Triccas
Sydney Institute for Infectious Diseases and the Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales, Australia
Stuart Tangye
Garvan Institute of Medical Research, Sydney, New South Wales, Australia
Nathan W. Bartlett
Hunter Medical Research Institute, University of Newcastle, Callaghan, Australia
David Darley
St Vincent's Hospital, Sydney, New South Wales, Australia
Gail Matthews
The Kirby Institute, University of New South Wales, New South Wales, Australia; St Vincent's Hospital, Sydney, New South Wales, Australia
Damien J. Stark
Molecular Diagnostic Medicine Laboratory, Sydpath, St Vincent's Hospital, Sydney, New South Wales, Australia
Kathy Petoumenos
The Kirby Institute, University of New South Wales, New South Wales, Australia
William D. Rawlinson
Serology and Virology Division (SAViD), NSW Health Pathology, Randwick, Australia
Ben Murrell
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden
Fabienne Brilot
Brain Autoimmunity Group, Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, School of Medical Sciences, New South Wales, Australia
Anthony L. Cunningham
The Westmead Institute for Medical Research, Westmead, New South Wales, Australia
Anthony D. Kelleher
The Kirby Institute, University of New South Wales, New South Wales, Australia; St Vincent's Hospital, Sydney, New South Wales, Australia
Anupriya Aggarwal
The Kirby Institute, University of New South Wales, New South Wales, Australia
Stuart G. Turville
The Kirby Institute, University of New South Wales, New South Wales, Australia; Corresponding author. The Kirby Institute, UNSW Australia, Office 529 Level 5 Wallace Wurth Building, UNSW, Sydney, NSW 2052, Australia.
Summary: Background: The Omicron era of the COVID-19 pandemic commenced at the beginning of 2022 and whilst it started with primarily BA.1, it was latter dominated by BA.2 and the related sub-lineage BA.5. Following resolution of the global BA.5 wave, a diverse grouping of Omicron sub-lineages emerged derived from BA.2, BA.5 and recombinants thereof. Whilst emerging from distinct lineages, all shared similar changes in the Spike glycoprotein affording them an outgrowth advantage through evasion of neutralising antibodies. Methods: Over the course of 2022, we monitored the potency and breadth of antibody neutralization responses to many emerging variants in the Australian community at three levels: (i) we tracked over 420,000 U.S. plasma donors over time through various vaccine booster roll outs and Omicron waves using sequentially collected IgG pools; (ii) we mapped the antibody response in individuals using blood from stringently curated vaccine and convalescent cohorts. (iii) finally we determine the in vitro efficacy of clinically approved therapies Evusheld and Sotrovimab. Findings: In pooled IgG samples, we observed the maturation of neutralization breadth to Omicron variants over time through continuing vaccine and infection waves. Importantly, in many cases, we observed increased antibody breadth to variants that were yet to be in circulation. Determination of viral neutralization at the cohort level supported equivalent coverage across prior and emerging variants with isolates BQ.1.1, XBB.1, BR.2.1 and XBF the most evasive. Further, these emerging variants were resistant to Evusheld, whilst increasing neutralization resistance to Sotrovimab was restricted to BQ.1.1 and XBF. We conclude at this current point in time that dominant variants can evade antibodies at levels equivalent to their most evasive lineage counterparts but sustain an entry phenotype that continues to promote an additional outgrowth advantage. In Australia, BR.2.1 and XBF share this phenotype and, in contrast to global variants, are uniquely dominant in this region in the later months of 2022. Interpretation: Whilst the appearance of a diverse range of omicron lineages has led to primary or partial resistance to clinically approved monoclonal antibodies, the maturation of the antibody response across both cohorts and a large donor pools importantly observes increasing breadth in the antibody neutralisation responses over time with a trajectory that covers both current and known emerging variants. Funding: This work was primarily supported by Australian Medical Foundation research grants MRF2005760 (SGT, GM & WDR), Medical Research Future Fund Antiviral Development Call grant (WDR), the New South Wales Health COVID-19 Research Grants Round 2 (SGT & FB) and the NSW Vaccine Infection and Immunology Collaborative (VIIM) (ALC). Variant modeling was supported by funding from SciLifeLab's Pandemic Laboratory Preparedness program to B.M. (VC-2022-0028) and by the European Union's Horizon 2020 research and innovation programme under grant agreement no. 101003653 (CoroNAb) to B.M.
