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Maintenance of Broad Neutralising Antibodies and Memory B Cells 12 Months Post-Infection Is Predicted by SARS-CoV-2 Specific CD4+ T Cell Responses

54 Pages Posted: 9 Sep 2021 Publication Status: Published

See all articles by Harikrishnan Balachandran

Harikrishnan Balachandran

University of New South Wales (UNSW) - School of Medical Sciences (SoMS)

Chansavath Phetsouphanh

University of New South Wales (UNSW) - Kirby Institute

David Agapiou

University of New South Wales (UNSW) - Kirby Institute

Anurag Adhikari

University of New South Wales (UNSW) - School of Medical Sciences (SoMS)

Chaturaka Rodrigo

University of New South Wales (UNSW) - School of Medical Sciences (SoMS)

Mohamed Hammoud

University of New South Wales (UNSW) - Kirby Institute

Lok Bahadur Shrestha

University of New South Wales (UNSW); University of New South Wales (UNSW)

Elizabeth Keoshkerian

University of New South Wales (UNSW) - Kirby Institute

Money Gupta

University of New South Wales (UNSW) - School of Medical Sciences (SoMS)

Stuart Turville

University of New South Wales (UNSW) - Kirby Institute

Daniel Christ

Garvan Institute of Medical Research

Cecile King

Garvan Institute of Medical Research

Sarah Sasson

University of New South Wales (UNSW) - Kirby Institute

Adam Bartlett

University of New South Wales (UNSW) - The Kirby Institute

Branka Grubor-Bauk

University of Adelaide - Viral Immunology Group

William Rawlinson

Government of New South Wales - Virology Research Laboratory

Anupriya Aggarwal

University of New South Wales (UNSW) - Kirby Institute

Alberto Ospina Stella

affiliation not provided to SSRN

Vera Klemm

University of New South Wales (UNSW) - Kirby Institute

Michael M. Mina

Northern Beaches Hospital

Jeffrey J. Post

University of New South Wales (UNSW) - Prince of Wales Clinical School

Bernard Hudson

Royal North Shore Hospital

Nicky Gilroy

The University of Sydney - Westmead Hospital

Pam Konecny

St George Hospital

Golo Ahlenstiel

Western Sydney University

Dominic Dwyer

The University of Sydney - Westmead Hospital

Tania C. Sorrell

The University of Sydney

Anthony Kelleher

University of New South Wales (UNSW) - Kirby Institute

Nicodemus Tedla

University of New South Wales (UNSW) - School of Medical Sciences (SoMS)

Andrew R. Lloyd

University of New South Wales (UNSW) - Kirby Institute

Marianne Martinello

University of New South Wales (UNSW) - Kirby Institute; University of New South Wales (UNSW) - St Vincent’s Hospital; South Western Sydney Local Health District - Blacktown & Mount Druitt Hospital

Rowena Anne Bull

University of New South Wales (UNSW) - Kirby Institute; University of New South Wales (UNSW) - School of Medical Sciences (SoMS)

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Abstract

Understanding the long-term maintenance of SARS-CoV-2 immunity is critical for prediction of protection against reinfection. In a cohort of 24 participants, the association of disease severity and early immunological measurements on the maintenance of humoral immune responses 12 months post-infection were examined. All severely affected participants maintained a stable subset of SARS-CoV-2 receptor-binding domain (RBD) specific memory B cells (MBCs) and good neutralising antibody breadth against the majority of the variants of concern, including the Delta variant. Modelling these immune responses on vaccine efficacy data indicated a level equivalent to a vaccine efficacy of approximately 45-76% against symptomatic reinfection (variant dependent). Overall, these findings indicate durable humoral responses in most participants, provide an estimate of the level of protection and identifies the magnitude and phenotype of baseline antigen-specific CD4+ T cell response as a predictor of maintenance of both antibody neutralisation breadth and RBD-specific MBC levels at 12 months post-infection.

Funding: The Kirby Institute is funded by the Australian Government Department of Health and Ageing. The views expressed in this publication do not necessarily represent the position of the Australian Government. Research reported in this publication was supported by Snow Medical Foundation as an investigator-initiated study. The content is solely the responsibility of the authors. RAB, MM, CR and ARL are fellows funded by National Health and Medical Research Council (NHMRC). MWAC is in part funded by the Research Infrastructure Programme of UNSW.

Declaration of Interests: The authors declare no competing interests.

Ethics Approval Statement: The protocol was approved by the Human Research Ethics Committees of the Northern Sydney Local Health District and the University of New South Wales, NSW Australia (ETH00520) and was conducted according to the Declaration of Helsinki and International Conference on Harmonization Good Clinical Practice (ICH/GCP) guidelines and local regulatory requirements. Written informed consent was obtained from all participants before study procedures.

Keywords: SARS-CoV-2, 12 months after SARS-CoV-2 infection, RBD-specific memory B cells, protection efficacy prediction, SARS-CoV-2 antibodies, SARS-CoV-2 neutralisation, variants of concern, Delta variant

Suggested Citation

Balachandran, Harikrishnan and Phetsouphanh, Chansavath and Agapiou, David and Adhikari, Anurag and Rodrigo, Chaturaka and Hammoud, Mohamed and Shrestha, Lok Bahadur and Keoshkerian, Elizabeth and Gupta, Money and Turville, Stuart and Christ, Daniel and King, Cecile and Sasson, Sarah and Bartlett, Adam and Grubor-Bauk, Branka and Rawlinson, William and Aggarwal, Anupriya and Stella, Alberto Ospina and Klemm, Vera and Mina, Michael M. and Post, Jeffrey J. and Hudson, Bernard and Gilroy, Nicky and Konecny, Pam and Ahlenstiel, Golo and Dwyer, Dominic and Sorrell, Tania C. and Kelleher, Anthony and Tedla, Nicodemus and Lloyd, Andrew R. and Martinello, Marianne and Bull, Rowena Anne, Maintenance of Broad Neutralising Antibodies and Memory B Cells 12 Months Post-Infection Is Predicted by SARS-CoV-2 Specific CD4+ T Cell Responses. Available at SSRN: https://ssrn.com/abstract=3920641 or http://dx.doi.org/10.2139/ssrn.3920641
This version of the paper has not been formally peer reviewed.

Harikrishnan Balachandran

University of New South Wales (UNSW) - School of Medical Sciences (SoMS) ( email )

Wallace Wurth Building
Sydney, NSW 2052
Australia

Chansavath Phetsouphanh

University of New South Wales (UNSW) - Kirby Institute ( email )

Sydney
Australia

David Agapiou

University of New South Wales (UNSW) - Kirby Institute ( email )

Sydney
Australia

Anurag Adhikari

University of New South Wales (UNSW) - School of Medical Sciences (SoMS) ( email )

Wallace Wurth Building
Sydney, NSW 2052
Australia

Chaturaka Rodrigo

University of New South Wales (UNSW) - School of Medical Sciences (SoMS) ( email )

Wallace Wurth Building
Sydney, NSW 2052
Australia

Mohamed Hammoud

University of New South Wales (UNSW) - Kirby Institute ( email )

Sydney
Australia

Lok Bahadur Shrestha

University of New South Wales (UNSW) ( email )

Disability Innovation Institute
UNSW, Randwick
Sydney, 2052
Australia

University of New South Wales (UNSW) ( email )

Disability Innovation Institute
UNSW, Randwick
Sydney, 2052
Australia

Elizabeth Keoshkerian

University of New South Wales (UNSW) - Kirby Institute ( email )

Sydney
Australia

Money Gupta

University of New South Wales (UNSW) - School of Medical Sciences (SoMS) ( email )

Wallace Wurth Building
Sydney, NSW 2052
Australia

Stuart Turville

University of New South Wales (UNSW) - Kirby Institute ( email )

Sydney
Australia

Daniel Christ

Garvan Institute of Medical Research ( email )

384 VICTORIA STREET
Darlinghurst, New South Wales 2010
Australia

Cecile King

Garvan Institute of Medical Research ( email )

384 VICTORIA STREET
Darlinghurst, New South Wales 2010
Australia

Sarah Sasson

University of New South Wales (UNSW) - Kirby Institute ( email )

Sydney
Australia

Adam Bartlett

University of New South Wales (UNSW) - The Kirby Institute ( email )

Branka Grubor-Bauk

University of Adelaide - Viral Immunology Group ( email )

Adelaide Medical School, FHMS
Adelaide, South Australia 5005
Australia

William Rawlinson

Government of New South Wales - Virology Research Laboratory ( email )

Anupriya Aggarwal

University of New South Wales (UNSW) - Kirby Institute ( email )

Sydney
Australia

Alberto Ospina Stella

affiliation not provided to SSRN

No Address Available

Vera Klemm

University of New South Wales (UNSW) - Kirby Institute ( email )

Sydney
Australia

Michael M. Mina

Northern Beaches Hospital ( email )

Australia

Jeffrey J. Post

University of New South Wales (UNSW) - Prince of Wales Clinical School ( email )

Australia

Bernard Hudson

Royal North Shore Hospital ( email )

Reserve Rd
St Leonards NSW 2065
Australia

Nicky Gilroy

The University of Sydney - Westmead Hospital ( email )

Hawkesbury Rd & Darcy Road
Westmead NSW 2145
Australia

Pam Konecny

St George Hospital ( email )

Australia

Golo Ahlenstiel

Western Sydney University ( email )

PO Box 10
Kingswood, NSW 2747
Australia

Dominic Dwyer

The University of Sydney - Westmead Hospital ( email )

Hawkesbury Rd & Darcy Road
Westmead NSW 2145
Australia

Tania C. Sorrell

The University of Sydney ( email )

University of Sydney
Sydney, NSW 2006
Australia

Anthony Kelleher

University of New South Wales (UNSW) - Kirby Institute ( email )

Sydney
Australia

Nicodemus Tedla

University of New South Wales (UNSW) - School of Medical Sciences (SoMS) ( email )

Wallace Wurth Building
Sydney, NSW 2052
Australia

Andrew R. Lloyd

University of New South Wales (UNSW) - Kirby Institute ( email )

Sydney
Australia

Marianne Martinello

University of New South Wales (UNSW) - Kirby Institute ( email )

Sydney
Australia

University of New South Wales (UNSW) - St Vincent’s Hospital ( email )

390 Victoria St
Darlinghurst, Sydney NSW 2010
Australia

South Western Sydney Local Health District - Blacktown & Mount Druitt Hospital ( email )

Blacktown
Australia

Rowena Anne Bull (Contact Author)

University of New South Wales (UNSW) - Kirby Institute ( email )

University of New South Wales (UNSW) - School of Medical Sciences (SoMS) ( email )

Wallace Wurth Building
Sydney, NSW 2052
Australia

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