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

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. ReddiDavid Shaw, Chuan Kok-Lim, Michael R. Beard, Daniela Weiskopf, Alessandro Sette, Stuart G. Turville, Rowena A. Bull, Simon C. Barry, Branka Grubor-Bauk

Research output: Contribution to journal › Article › peer-review

18 Citations (Scopus)

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.

Original language	English
Article number	100651
Journal	Cell Reports Medicine
Volume	3
Issue number	6
DOIs	https://doi.org/10.1016/j.xcrm.2022.100651
Publication status	Published or Issued - 21 Jun 2022

Keywords

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

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.xcrm.2022.100651

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Garcia-Valtanen, P., Hope, C. M., Masavuli, M. G., Yeow, A. E. L., Balachandran, H., Mekonnen, Z. A., Al-Delfi, Z., Abayasingam, A., Agapiou, D., Stella, A. O., Aggarwal, A., Bouras, G., Gummow, J., Ferguson, C., O'Connor, S., McCartney, E. M., Lynn, D. J., Maddern, G., Gowans, E. J., ... Grubor-Bauk, B. (2022). SARS-CoV-2 Omicron variant escapes neutralizing antibodies and T cell responses more efficiently than other variants in mild COVID-19 convalescents. Cell Reports Medicine, 3(6), [100651]. https://doi.org/10.1016/j.xcrm.2022.100651

@article{35fa30fd8d7843dcb56e6cec836ba194,

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

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 = "antibody response, antigen drift, memory B cells, SARS-CoV-2, T cell immunity, Variant of Concern, virus neutralization",

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

note = "Funding Information: This work was funded by project grants from The Hospital Research Foundation and Women's and Children's Hospital Foundation, Adelaide, Australia. M.G.M. is a THRF Early Career Fellow. B.G.-B. is a THRF Mid-Career Fellow. We would like to thank Ms. Suzanne Edwards, University of Adelaide, for statistical advice and analysis. This project has been supported partly with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract nos. 75N93021C00016 to A.S. and 75N9301900065 to A.S. and D.W. Writing original manuscript draft, P.G.-V. B.G.-B. and M.G.M.; editing manuscript, S.C.B. C.M.H. M.R.B. C.K.-L. E.J.G. G.M. and D.J.L.; design of experiments, P.G.-V. C.M.H. M.G.M. A.S. D.W. S.G.T. B.G.-B. S.C.B. and R.A.B.; performed experiments, P.G.-V. C.M.H. M.G.M. A.E.L.Y. H.B. Z.A.M. Z.A.-D. A. Abayasingam, A.O.S. A. Aggarwal, and D.A.; data analysis, P.G.-V. C.M.H. A.E.L.Y. G.B. B.G.-B. and R.A.B.; patient sample collection, C.M.H. J.G. C.F. S.O. E.M.M. B.A.J.R. D.S. and C.K.-L. All authors reviewed, discussed, and agreed with the manuscript. A.S. is currently a consultant for Gritstone, Flow Pharma, Arcturus, Epitogenesis, Oxfordimmunotech, Caprion, and Avalia. La Jolla Institute for Immunology (A.S. and D.W.) has filed for patent protection for various aspects of T cell epitope and vaccine design work. P.G.-V. C.M.H. M.G.M. A.E.L.Y. H.B. Z.A.M. Z.A.-D. A. Abayasingam, D.A. A.O.S. A. Aggarwal, G.B. J.G. C.F. S.O. E.M.M. D.J.L. G.M. E.J.G. B.A.J.R. D.S. C.K.-L. S.G.T. M.R.B. D.W. R.A.B. S.C.B. and B.G.-B. declare no conflicts of interest. Inclusion of investigators and the assignment of their roles and authorship in this study was done based on their qualifications and research experience and without discriminating based on ethnic, gender, sexual orientation, or religious belief as mandated by Australian law and in conformity with the Australian Code for the Responsible Conduct of Research and the core ethical principles of the institutions involved. Funding Information: This work was funded by project grants from The Hospital Research Foundation and Women's and Children's Hospital Foundation , Adelaide, Australia. M.G.M. is a THRF Early Career Fellow. B.G.-B. is a THRF Mid-Career Fellow. We would like to thank Ms. Suzanne Edwards, University of Adelaide, for statistical advice and analysis. This project has been supported partly with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health , Department of Health and Human Services , under contract nos. 75N93021C00016 to A.S. and 75N9301900065 to A.S. and D.W. Publisher Copyright: {\textcopyright} 2022 The Author(s)",

year = "2022",

month = jun,

day = "21",

doi = "10.1016/j.xcrm.2022.100651",

language = "English",

volume = "3",

journal = "Cell Reports Medicine",

issn = "2666-3791",

publisher = "Cell Press",

number = "6",

}

Garcia-Valtanen, P, Hope, CM, Masavuli, MG, Yeow, AEL, Balachandran, H, Mekonnen, ZA, Al-Delfi, Z, Abayasingam, A, Agapiou, D, Stella, AO, Aggarwal, A, Bouras, G, Gummow, J, Ferguson, C, O'Connor, S, McCartney, EM, Lynn, DJ, Maddern, G, Gowans, EJ, Reddi, BAJ, Shaw, D, Kok-Lim, C, Beard, MR, Weiskopf, D, Sette, A, Turville, SG, Bull, RA, Barry, SC & Grubor-Bauk, B 2022, 'SARS-CoV-2 Omicron variant escapes neutralizing antibodies and T cell responses more efficiently than other variants in mild COVID-19 convalescents', Cell Reports Medicine, vol. 3, no. 6, 100651. https://doi.org/10.1016/j.xcrm.2022.100651

TY - JOUR

T1 - SARS-CoV-2 Omicron variant escapes neutralizing antibodies and T cell responses more efficiently than other variants in mild COVID-19 convalescents

AU - Garcia-Valtanen, Pablo

AU - Hope, Christopher M.

AU - Masavuli, Makutiro G.

AU - Yeow, Arthur Eng Lip

AU - Balachandran, Harikrishnan

AU - Mekonnen, Zelalem A.

AU - Al-Delfi, Zahraa

AU - Abayasingam, Arunasingam

AU - Agapiou, David

AU - Stella, Alberto Ospina

AU - Aggarwal, Anupriya

AU - Bouras, George

AU - Gummow, Jason

AU - Ferguson, Catherine

AU - O'Connor, Stephanie

AU - McCartney, Erin M.

AU - Lynn, David J.

AU - Maddern, Guy

AU - Gowans, Eric J.

AU - Reddi, Benjamin A.J.

AU - Shaw, David

AU - Kok-Lim, Chuan

AU - Beard, Michael R.

AU - Weiskopf, Daniela

AU - Sette, Alessandro

AU - Turville, Stuart G.

AU - Bull, Rowena A.

AU - Barry, Simon C.

AU - Grubor-Bauk, Branka

N1 - Funding Information: This work was funded by project grants from The Hospital Research Foundation and Women's and Children's Hospital Foundation, Adelaide, Australia. M.G.M. is a THRF Early Career Fellow. B.G.-B. is a THRF Mid-Career Fellow. We would like to thank Ms. Suzanne Edwards, University of Adelaide, for statistical advice and analysis. This project has been supported partly with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract nos. 75N93021C00016 to A.S. and 75N9301900065 to A.S. and D.W. Writing original manuscript draft, P.G.-V. B.G.-B. and M.G.M.; editing manuscript, S.C.B. C.M.H. M.R.B. C.K.-L. E.J.G. G.M. and D.J.L.; design of experiments, P.G.-V. C.M.H. M.G.M. A.S. D.W. S.G.T. B.G.-B. S.C.B. and R.A.B.; performed experiments, P.G.-V. C.M.H. M.G.M. A.E.L.Y. H.B. Z.A.M. Z.A.-D. A. Abayasingam, A.O.S. A. Aggarwal, and D.A.; data analysis, P.G.-V. C.M.H. A.E.L.Y. G.B. B.G.-B. and R.A.B.; patient sample collection, C.M.H. J.G. C.F. S.O. E.M.M. B.A.J.R. D.S. and C.K.-L. All authors reviewed, discussed, and agreed with the manuscript. A.S. is currently a consultant for Gritstone, Flow Pharma, Arcturus, Epitogenesis, Oxfordimmunotech, Caprion, and Avalia. La Jolla Institute for Immunology (A.S. and D.W.) has filed for patent protection for various aspects of T cell epitope and vaccine design work. P.G.-V. C.M.H. M.G.M. A.E.L.Y. H.B. Z.A.M. Z.A.-D. A. Abayasingam, D.A. A.O.S. A. Aggarwal, G.B. J.G. C.F. S.O. E.M.M. D.J.L. G.M. E.J.G. B.A.J.R. D.S. C.K.-L. S.G.T. M.R.B. D.W. R.A.B. S.C.B. and B.G.-B. declare no conflicts of interest. Inclusion of investigators and the assignment of their roles and authorship in this study was done based on their qualifications and research experience and without discriminating based on ethnic, gender, sexual orientation, or religious belief as mandated by Australian law and in conformity with the Australian Code for the Responsible Conduct of Research and the core ethical principles of the institutions involved. Funding Information: This work was funded by project grants from The Hospital Research Foundation and Women's and Children's Hospital Foundation , Adelaide, Australia. M.G.M. is a THRF Early Career Fellow. B.G.-B. is a THRF Mid-Career Fellow. We would like to thank Ms. Suzanne Edwards, University of Adelaide, for statistical advice and analysis. This project has been supported partly with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health , Department of Health and Human Services , under contract nos. 75N93021C00016 to A.S. and 75N9301900065 to A.S. and D.W. Publisher Copyright: © 2022 The Author(s)

PY - 2022/6/21

Y1 - 2022/6/21

N2 - 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.

AB - 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.

KW - antibody response

KW - antigen drift

KW - memory B cells

KW - SARS-CoV-2

KW - T cell immunity

KW - Variant of Concern

KW - virus neutralization

UR - http://www.scopus.com/inward/record.url?scp=85131242045&partnerID=8YFLogxK

U2 - 10.1016/j.xcrm.2022.100651

DO - 10.1016/j.xcrm.2022.100651

M3 - Article

C2 - 35654046

AN - SCOPUS:85131242045

SN - 2666-3791

VL - 3

JO - Cell Reports Medicine

JF - Cell Reports Medicine

IS - 6

M1 - 100651

ER -

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

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Keywords

ASJC Scopus subject areas

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