SARS-CoV-2 Omicron variant escapes neutralizing antibodies and T cell responses more efficiently than other variants in mild COVID-19 convalescents

Pablo Garcia-Valtanen; Christopher M Hope; Makutiro G Masavuli; Arthur Eng Lip Yeow; Harikrishnan Balachandran; Zelalem A Mekonnen; Zahraa Al-Delfi; Arunasingam Abayasingam; David Agapiou; Alberto Ospina Stella; Anupriya Aggarwal; George Bouras; Jason Gummow; Catherine Ferguson; Stephanie O'Connor; Erin M McCartney; David J Lynn; Guy Maddern; Eric J Gowans; Benjamin A J Reddi; David Shaw; Chuan Kok-Lim; Michael R Beard; Daniela Weiskopf; Alessandro Sette; Stuart G Turville; Rowena A Bull; Simon C Barry; Branka Grubor-Bauk

doi:10.1016/j.xcrm.2022.100651

SARS-CoV-2 Omicron variant escapes neutralizing antibodies and T cell responses more efficiently than other variants in mild COVID-19 convalescents

Cell Rep Med. 2022 Jun 21;3(6):100651. doi: 10.1016/j.xcrm.2022.100651. Epub 2022 May 17.

Authors

Pablo Garcia-Valtanen¹, Christopher M Hope², Makutiro G Masavuli¹, Arthur Eng Lip Yeow¹, Harikrishnan Balachandran³, Zelalem A Mekonnen¹, Zahraa Al-Delfi¹, Arunasingam Abayasingam³, David Agapiou³, Alberto Ospina Stella⁴, Anupriya Aggarwal⁴, George Bouras⁵, Jason Gummow⁶, Catherine Ferguson⁷, Stephanie O'Connor⁸, Erin M McCartney⁷, David J Lynn⁹, Guy Maddern¹⁰, Eric J Gowans¹, Benjamin A J Reddi⁸, David Shaw⁷, Chuan Kok-Lim¹¹, Michael R Beard¹², Daniela Weiskopf¹³, Alessandro Sette¹⁴, Stuart G Turville⁴, Rowena A Bull³, Simon C Barry¹⁵, Branka Grubor-Bauk¹⁶

Affiliations

¹ Viral Immunology Group, Adelaide Medical School, University of Adelaide and Basil Hetzel Institute for Translational Health Research, Adelaide, SA, Australia.
² Molecular Immunology, Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia; Women's and Children's Health Network, North Adelaide, SA, Australia.
³ School of Medical Sciences, Faculty of Medicine, UNSW, Australia, Sydney, NSW, Australia.
⁴ The Kirby Institute, The University of New South Wales, Sydney, NSW, Australia.
⁵ Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA, Australia; The Department of Surgery - Otolaryngology, Head and Neck Surgery, University of Adelaide and the Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Woodville South, SA, Australia.
⁶ Gene Silencing and Expression Core Facility, Adelaide Health and Medical Sciences, Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia.
⁷ Infectious Diseases Department, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, SA, Australia.
⁸ Intensive Care Unit, Royal Adelaide Hospital, Central Adelaide Local Health Network and Adelaide Medical School, University of Adelaide, Adelaide, SA, Australia.
⁹ Precision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, SA 5001, Australia; Flinders Health and Medical Research Institute, Flinders University, Bedford Park, SA 5042, Australia.
¹⁰ Discipline of Surgery, The University of Adelaide, Adelaide, SA 5000, Australia.
¹¹ Gene Silencing and Expression Core Facility, Adelaide Health and Medical Sciences, Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia; Microbiology and Infectious Diseases Department, SA Pathology, Adelaide, SA, Australia; Research Centre for Infectious Diseases, School of Biological Sciences, The University of Adelaide, Adelaide, SA, Australia.
¹² Research Centre for Infectious Diseases, School of Biological Sciences, The University of Adelaide, Adelaide, SA, Australia.
¹³ Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA, USA.
¹⁴ Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA, USA.
¹⁵ Molecular Immunology, Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia; Women's and Children's Health Network, North Adelaide, SA, Australia. Electronic address: simon.barry@adelaide.edu.au.
¹⁶ Viral Immunology Group, Adelaide Medical School, University of Adelaide and Basil Hetzel Institute for Translational Health Research, Adelaide, SA, Australia. Electronic address: branka.grubor@adelaide.edu.au.

Abstract

Coronavirus disease 2019 (COVID-19) convalescents living in regions with low vaccination rates rely on post-infection immunity for protection against re-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluate humoral and T cell immunity against five variants of concern (VOCs) in mild-COVID-19 convalescents at 12 months after infection with ancestral virus. In this cohort, ancestral, receptor-binding domain (RBD)-specific antibody and circulating memory B cell levels are conserved in most individuals, and yet serum neutralization against live B.1.1.529 (Omicron) is completely abrogated and significantly reduced for other VOCs. Likewise, ancestral SARS-CoV-2-specific memory T cell frequencies are maintained in >50% of convalescents, but the cytokine response in these cells to mutated spike epitopes corresponding to B.1.1.529 and B.1.351 (Beta) VOCs were impaired. These results indicate that increased antigen variability in VOCs impairs humoral and spike-specific T cell immunity post-infection, strongly suggesting that COVID-19 convalescents are vulnerable and at risk of re-infection with VOCs, thus stressing the importance of vaccination programs.

Keywords: SARS-CoV-2; T cell immunity; Variant of Concern; antibody response; antigen drift; memory B cells; virus neutralization.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Antibodies, Neutralizing
Antibodies, Viral
COVID-19*
Humans
Reinfection
SARS-CoV-2 / genetics
Spike Glycoprotein, Coronavirus / genetics
T-Lymphocytes*

Substances

Antibodies, Neutralizing
Antibodies, Viral
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2

Supplementary concepts

SARS-CoV-2 variants

Grants and funding

75N93021C00016/AI/NIAID NIH HHS/United States