Durable reprogramming of neutralizing antibody responses following Omicron breakthrough infection

Wen Shi Lee; Hyon-Xhi Tan; Arnold Reynaldi; Robyn Esterbauer; Marios Koutsakos; Julie Nguyen; Thakshila Amarasena; Helen E Kent; Anupriya Aggarwal; Stuart G Turville; George Taiaroa; Paul Kinsella; Kwee Chin Liew; Thomas Tran; Deborah A Williamson; Deborah Cromer; Miles P Davenport; Stephen J Kent; Jennifer A Juno; David S Khoury; Adam K Wheatley

doi:10.1126/sciadv.adg5301

Durable reprogramming of neutralizing antibody responses following Omicron breakthrough infection

Wen Shi Lee, Hyon-Xhi Tan, Arnold Reynaldi, Robyn Esterbauer, Marios Koutsakos, Julie Nguyen, Thakshila Amarasena, Helen E Kent, Anupriya Aggarwal, Stuart G Turville, George Taiaroa, Paul Kinsella, Kwee Chin Liew, Thomas Tran, Deborah A Williamson, Deborah Cromer, Miles P Davenport, Stephen J Kent, Jennifer A Juno, David S KhouryAdam K Wheatley^*

^*Corresponding author for this work

School of Medicine

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

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection of vaccinated individuals is increasingly common with the circulation of highly immune evasive and transmissible Omicron variants. Here, we report the dynamics and durability of recalled spike-specific humoral immunity following Omicron BA.1 or BA.2 breakthrough infection, with longitudinal sampling up to 8 months after infection. Both BA.1 and BA.2 infections robustly boosted neutralization activity against the infecting strain while expanding breadth against BA.4, although neutralization activity was substantially reduced for the more recent XBB and BQ.1.1 strains. Cross-reactive memory B cells against both ancestral and Omicron spike were predominantly expanded by infection, with limited recruitment of de novo Omicron-specific B cells or antibodies. Modeling of neutralization titers predicts that protection from symptomatic reinfection against antigenically similar strains will be durable but is undermined by new emerging strains with further neutralization escape.

Original language	English
Article number	eadg5301
Pages (from-to)	1-11
Number of pages	11
Journal	Science Advances
Volume	9
Issue number	29
Early online date	21 Jul 2023
DOIs	https://doi.org/10.1126/sciadv.adg5301
Publication status	Published - Jul 2023

Keywords

Humans
Antibodies, Neutralizing
Breakthrough infections
COVID-19
SARS-CoV-2

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Lee, W. S., Tan, H.-X., Reynaldi, A., Esterbauer, R., Koutsakos, M., Nguyen, J., Amarasena, T., Kent, H. E., Aggarwal, A., Turville, S. G., Taiaroa, G., Kinsella, P., Liew, K. C., Tran, T., Williamson, D. A., Cromer, D., Davenport, M. P., Kent, S. J., Juno, J. A., ... Wheatley, A. K. (2023). Durable reprogramming of neutralizing antibody responses following Omicron breakthrough infection. Science Advances, 9(29), 1-11. Article eadg5301. https://doi.org/10.1126/sciadv.adg5301

@article{7beef9e942b64cbb8b208d2c58c20f53,

title = "Durable reprogramming of neutralizing antibody responses following Omicron breakthrough infection",

abstract = "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection of vaccinated individuals is increasingly common with the circulation of highly immune evasive and transmissible Omicron variants. Here, we report the dynamics and durability of recalled spike-specific humoral immunity following Omicron BA.1 or BA.2 breakthrough infection, with longitudinal sampling up to 8 months after infection. Both BA.1 and BA.2 infections robustly boosted neutralization activity against the infecting strain while expanding breadth against BA.4, although neutralization activity was substantially reduced for the more recent XBB and BQ.1.1 strains. Cross-reactive memory B cells against both ancestral and Omicron spike were predominantly expanded by infection, with limited recruitment of de novo Omicron-specific B cells or antibodies. Modeling of neutralization titers predicts that protection from symptomatic reinfection against antigenically similar strains will be durable but is undermined by new emerging strains with further neutralization escape.",

keywords = "Humans, Antibodies, Neutralizing, Breakthrough infections, COVID-19, SARS-CoV-2",

author = "Lee, {Wen Shi} and Hyon-Xhi Tan and Arnold Reynaldi and Robyn Esterbauer and Marios Koutsakos and Julie Nguyen and Thakshila Amarasena and Kent, {Helen E} and Anupriya Aggarwal and Turville, {Stuart G} and George Taiaroa and Paul Kinsella and Liew, {Kwee Chin} and Thomas Tran and Williamson, {Deborah A} and Deborah Cromer and Davenport, {Miles P} and Kent, {Stephen J} and Juno, {Jennifer A} and Khoury, {David S} and Wheatley, {Adam K}",

note = "Funding: This work was supported by Australian National Health and Medical Research Council grants 1149990, 1162760, and 2004398; Australian Medical Research Future Fund grants 2005544 and 2013870; the Victorian government; Australian National Health and Medical Research Council Investigator or Fellowship grants (H.-X.T., M.K., D.A.W., M.P.D., S.J.K., J.A.J., and A.K.W.); and Melbourne Postdoctoral Fellowship (W.S.L.).",

year = "2023",

month = jul,

doi = "10.1126/sciadv.adg5301",

language = "English",

volume = "9",

pages = "1--11",

journal = "Science Advances",

issn = "2375-2548",

publisher = "American Association for the Advancement of Science",

number = "29",

}

Lee, WS, Tan, H-X, Reynaldi, A, Esterbauer, R, Koutsakos, M, Nguyen, J, Amarasena, T, Kent, HE, Aggarwal, A, Turville, SG, Taiaroa, G, Kinsella, P, Liew, KC, Tran, T, Williamson, DA, Cromer, D, Davenport, MP, Kent, SJ, Juno, JA, Khoury, DS & Wheatley, AK 2023, 'Durable reprogramming of neutralizing antibody responses following Omicron breakthrough infection', Science Advances, vol. 9, no. 29, eadg5301, pp. 1-11. https://doi.org/10.1126/sciadv.adg5301

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T1 - Durable reprogramming of neutralizing antibody responses following Omicron breakthrough infection

AU - Lee, Wen Shi

AU - Tan, Hyon-Xhi

AU - Reynaldi, Arnold

AU - Esterbauer, Robyn

AU - Koutsakos, Marios

AU - Nguyen, Julie

AU - Amarasena, Thakshila

AU - Kent, Helen E

AU - Aggarwal, Anupriya

AU - Turville, Stuart G

AU - Taiaroa, George

AU - Kinsella, Paul

AU - Liew, Kwee Chin

AU - Tran, Thomas

AU - Williamson, Deborah A

AU - Cromer, Deborah

AU - Davenport, Miles P

AU - Kent, Stephen J

AU - Juno, Jennifer A

AU - Khoury, David S

AU - Wheatley, Adam K

N1 - Funding: This work was supported by Australian National Health and Medical Research Council grants 1149990, 1162760, and 2004398; Australian Medical Research Future Fund grants 2005544 and 2013870; the Victorian government; Australian National Health and Medical Research Council Investigator or Fellowship grants (H.-X.T., M.K., D.A.W., M.P.D., S.J.K., J.A.J., and A.K.W.); and Melbourne Postdoctoral Fellowship (W.S.L.).

PY - 2023/7

Y1 - 2023/7

N2 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection of vaccinated individuals is increasingly common with the circulation of highly immune evasive and transmissible Omicron variants. Here, we report the dynamics and durability of recalled spike-specific humoral immunity following Omicron BA.1 or BA.2 breakthrough infection, with longitudinal sampling up to 8 months after infection. Both BA.1 and BA.2 infections robustly boosted neutralization activity against the infecting strain while expanding breadth against BA.4, although neutralization activity was substantially reduced for the more recent XBB and BQ.1.1 strains. Cross-reactive memory B cells against both ancestral and Omicron spike were predominantly expanded by infection, with limited recruitment of de novo Omicron-specific B cells or antibodies. Modeling of neutralization titers predicts that protection from symptomatic reinfection against antigenically similar strains will be durable but is undermined by new emerging strains with further neutralization escape.

AB - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection of vaccinated individuals is increasingly common with the circulation of highly immune evasive and transmissible Omicron variants. Here, we report the dynamics and durability of recalled spike-specific humoral immunity following Omicron BA.1 or BA.2 breakthrough infection, with longitudinal sampling up to 8 months after infection. Both BA.1 and BA.2 infections robustly boosted neutralization activity against the infecting strain while expanding breadth against BA.4, although neutralization activity was substantially reduced for the more recent XBB and BQ.1.1 strains. Cross-reactive memory B cells against both ancestral and Omicron spike were predominantly expanded by infection, with limited recruitment of de novo Omicron-specific B cells or antibodies. Modeling of neutralization titers predicts that protection from symptomatic reinfection against antigenically similar strains will be durable but is undermined by new emerging strains with further neutralization escape.

KW - Humans

KW - Antibodies, Neutralizing

KW - Breakthrough infections

KW - COVID-19

KW - SARS-CoV-2

U2 - 10.1126/sciadv.adg5301

DO - 10.1126/sciadv.adg5301

M3 - Article

C2 - 37478181

SN - 2375-2548

VL - 9

SP - 1

EP - 11

JO - Science Advances

JF - Science Advances

IS - 29

M1 - eadg5301

ER -

Durable reprogramming of neutralizing antibody responses following Omicron breakthrough infection

Abstract

Keywords

UN SDGs

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