Omicron infection following vaccination enhances a broad spectrum of immune responses dependent on infection history

Hailey Hornsby; Alexander R. Nicols; Stephanie Longet; Chang Liu; Adriana Tomic; Adrienn Angyal; Barbara Kronsteiner; Jessica K. Tyerman; Tom Tipton; Peijun Zhang; Marta Gallis; Piyada Supasa; Muneeswaran Selvaraj; Priyanka Abraham; Isabel Neale; Mohammad Ali; Natalie A. Barratt; Jeremy M. Nell; Lotta Gustafsson; Scarlett Strickland; Irina Grouneva; Timothy Rostron; Shona C. Moore; Luisa M. Hering; Susan L. Dobson; Sagida Bibi; Juthathip Mongkolsapaya; Teresa Lambe; Dan Wootton; Victoria Hall; Susan Hopkins; Tao Dong; Eleanor Barnes; Gavin Screaton; Alex Richter; Lance Turtle; Sarah L. Rowland-Jones; Miles Carroll; Christopher J. A. Duncan; Paul Klenerman; Susanna J. Dunachie; Rebecca P. Payne; Thushan I. de Silva

doi:10.1038/s41467-023-40592-4

Omicron infection following vaccination enhances a broad spectrum of immune responses dependent on infection history

Hailey Hornsby, Alexander R. Nicols, Stephanie Longet, Chang Liu, Adriana Tomic, Adrienn Angyal, Barbara Kronsteiner, Jessica K. Tyerman, Tom Tipton, Peijun Zhang, Marta Gallis, Piyada Supasa, Muneeswaran Selvaraj, Priyanka Abraham, Isabel Neale, Mohammad Ali, Natalie A. Barratt, Jeremy M. Nell, Lotta Gustafsson, Scarlett StricklandIrina Grouneva, Timothy Rostron, Shona C. Moore, Luisa M. Hering, Susan L. Dobson, Sagida Bibi, Juthathip Mongkolsapaya, Teresa Lambe, Dan Wootton, Victoria Hall, Susan Hopkins, Tao Dong, Eleanor Barnes, Gavin Screaton, Alex Richter, Lance Turtle, Sarah L. Rowland-Jones, Miles Carroll, Christopher J. A. Duncan, Paul Klenerman^*, Susanna J. Dunachie, Rebecca P. Payne, Thushan I. de Silva^*

^*Corresponding author for this work

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Abstract

Pronounced immune escape by the SARS-CoV-2 Omicron variant has resulted in many individuals possessing hybrid immunity, generated through a combination of vaccination and infection. Concerns have been raised that omicron breakthrough infections in triple-vaccinated individuals result in poor induction of omicron-specific immunity, and that prior SARS-CoV-2 infection is associated with immune dampening. Taking a broad and comprehensive approach, we characterize mucosal and blood immunity to spike and non-spike antigens following BA.1/BA.2 infections in triple mRNA-vaccinated individuals, with and without prior SARS-CoV-2 infection. We find that most individuals increase BA.1/BA.2/BA.5-specific neutralizing antibodies following infection, but confirm that the magnitude of increase and post-omicron titres are higher in the infection-naive. In contrast, significant increases in nasal responses, including neutralizing activity against BA.5 spike, are seen regardless of infection history. Spike-specific T cells increase only in infection-naive vaccinees; however, post-omicron T cell responses are significantly higher in the previously-infected, who display a maximally induced response with a highly cytotoxic CD8+ phenotype following their 3rd mRNA vaccine dose. Responses to non-spike antigens increase significantly regardless of prior infection status. These findings suggest that hybrid immunity induced by omicron breakthrough infections is characterized by significant immune enhancement that can help protect against future omicron variants.

Original language	English
Article number	5065
Number of pages	16
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-40592-4
Publication status	Published - 21 Aug 2023

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Hornsby, H., Nicols, A. R., Longet, S., Liu, C., Tomic, A., Angyal, A., Kronsteiner, B., Tyerman, J. K., Tipton, T., Zhang, P., Gallis, M., Supasa, P., Selvaraj, M., Abraham, P., Neale, I., Ali, M., Barratt, N. A., Nell, J. M., Gustafsson, L., ... de Silva, T. I. (2023). Omicron infection following vaccination enhances a broad spectrum of immune responses dependent on infection history. Nature Communications, 14(1), Article 5065. https://doi.org/10.1038/s41467-023-40592-4

@article{73ed72a85a0846ec84bdd9e8049802dc,

title = "Omicron infection following vaccination enhances a broad spectrum of immune responses dependent on infection history",

abstract = "Pronounced immune escape by the SARS-CoV-2 Omicron variant has resulted in many individuals possessing hybrid immunity, generated through a combination of vaccination and infection. Concerns have been raised that omicron breakthrough infections in triple-vaccinated individuals result in poor induction of omicron-specific immunity, and that prior SARS-CoV-2 infection is associated with immune dampening. Taking a broad and comprehensive approach, we characterize mucosal and blood immunity to spike and non-spike antigens following BA.1/BA.2 infections in triple mRNA-vaccinated individuals, with and without prior SARS-CoV-2 infection. We find that most individuals increase BA.1/BA.2/BA.5-specific neutralizing antibodies following infection, but confirm that the magnitude of increase and post-omicron titres are higher in the infection-naive. In contrast, significant increases in nasal responses, including neutralizing activity against BA.5 spike, are seen regardless of infection history. Spike-specific T cells increase only in infection-naive vaccinees; however, post-omicron T cell responses are significantly higher in the previously-infected, who display a maximally induced response with a highly cytotoxic CD8+ phenotype following their 3rd mRNA vaccine dose. Responses to non-spike antigens increase significantly regardless of prior infection status. These findings suggest that hybrid immunity induced by omicron breakthrough infections is characterized by significant immune enhancement that can help protect against future omicron variants.",

author = "Hailey Hornsby and Nicols, {Alexander R.} and Stephanie Longet and Chang Liu and Adriana Tomic and Adrienn Angyal and Barbara Kronsteiner and Tyerman, {Jessica K.} and Tom Tipton and Peijun Zhang and Marta Gallis and Piyada Supasa and Muneeswaran Selvaraj and Priyanka Abraham and Isabel Neale and Mohammad Ali and Barratt, {Natalie A.} and Nell, {Jeremy M.} and Lotta Gustafsson and Scarlett Strickland and Irina Grouneva and Timothy Rostron and Moore, {Shona C.} and Hering, {Luisa M.} and Dobson, {Susan L.} and Sagida Bibi and Juthathip Mongkolsapaya and Teresa Lambe and Dan Wootton and Victoria Hall and Susan Hopkins and Tao Dong and Eleanor Barnes and Gavin Screaton and Alex Richter and Lance Turtle and Rowland-Jones, {Sarah L.} and Miles Carroll and Duncan, {Christopher J. A.} and Paul Klenerman and Dunachie, {Susanna J.} and Payne, {Rebecca P.} and {de Silva}, {Thushan I.}",

year = "2023",

month = aug,

day = "21",

doi = "10.1038/s41467-023-40592-4",

language = "English",

volume = "14",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Springer",

number = "1",

}

Hornsby, H, Nicols, AR, Longet, S, Liu, C, Tomic, A, Angyal, A, Kronsteiner, B, Tyerman, JK, Tipton, T, Zhang, P, Gallis, M, Supasa, P, Selvaraj, M, Abraham, P, Neale, I, Ali, M, Barratt, NA, Nell, JM, Gustafsson, L, Strickland, S, Grouneva, I, Rostron, T, Moore, SC, Hering, LM, Dobson, SL, Bibi, S, Mongkolsapaya, J, Lambe, T, Wootton, D, Hall, V, Hopkins, S, Dong, T, Barnes, E, Screaton, G, Richter, A, Turtle, L, Rowland-Jones, SL, Carroll, M, Duncan, CJA, Klenerman, P, Dunachie, SJ, Payne, RP & de Silva, TI 2023, 'Omicron infection following vaccination enhances a broad spectrum of immune responses dependent on infection history', Nature Communications, vol. 14, no. 1, 5065. https://doi.org/10.1038/s41467-023-40592-4

TY - JOUR

T1 - Omicron infection following vaccination enhances a broad spectrum of immune responses dependent on infection history

AU - Hornsby, Hailey

AU - Nicols, Alexander R.

AU - Longet, Stephanie

AU - Liu, Chang

AU - Tomic, Adriana

AU - Angyal, Adrienn

AU - Kronsteiner, Barbara

AU - Tyerman, Jessica K.

AU - Tipton, Tom

AU - Zhang, Peijun

AU - Gallis, Marta

AU - Supasa, Piyada

AU - Selvaraj, Muneeswaran

AU - Abraham, Priyanka

AU - Neale, Isabel

AU - Ali, Mohammad

AU - Barratt, Natalie A.

AU - Nell, Jeremy M.

AU - Gustafsson, Lotta

AU - Strickland, Scarlett

AU - Grouneva, Irina

AU - Rostron, Timothy

AU - Moore, Shona C.

AU - Hering, Luisa M.

AU - Dobson, Susan L.

AU - Bibi, Sagida

AU - Mongkolsapaya, Juthathip

AU - Lambe, Teresa

AU - Wootton, Dan

AU - Hall, Victoria

AU - Hopkins, Susan

AU - Dong, Tao

AU - Barnes, Eleanor

AU - Screaton, Gavin

AU - Richter, Alex

AU - Turtle, Lance

AU - Rowland-Jones, Sarah L.

AU - Carroll, Miles

AU - Duncan, Christopher J. A.

AU - Klenerman, Paul

AU - Dunachie, Susanna J.

AU - Payne, Rebecca P.

AU - de Silva, Thushan I.

PY - 2023/8/21

Y1 - 2023/8/21

N2 - Pronounced immune escape by the SARS-CoV-2 Omicron variant has resulted in many individuals possessing hybrid immunity, generated through a combination of vaccination and infection. Concerns have been raised that omicron breakthrough infections in triple-vaccinated individuals result in poor induction of omicron-specific immunity, and that prior SARS-CoV-2 infection is associated with immune dampening. Taking a broad and comprehensive approach, we characterize mucosal and blood immunity to spike and non-spike antigens following BA.1/BA.2 infections in triple mRNA-vaccinated individuals, with and without prior SARS-CoV-2 infection. We find that most individuals increase BA.1/BA.2/BA.5-specific neutralizing antibodies following infection, but confirm that the magnitude of increase and post-omicron titres are higher in the infection-naive. In contrast, significant increases in nasal responses, including neutralizing activity against BA.5 spike, are seen regardless of infection history. Spike-specific T cells increase only in infection-naive vaccinees; however, post-omicron T cell responses are significantly higher in the previously-infected, who display a maximally induced response with a highly cytotoxic CD8+ phenotype following their 3rd mRNA vaccine dose. Responses to non-spike antigens increase significantly regardless of prior infection status. These findings suggest that hybrid immunity induced by omicron breakthrough infections is characterized by significant immune enhancement that can help protect against future omicron variants.

AB - Pronounced immune escape by the SARS-CoV-2 Omicron variant has resulted in many individuals possessing hybrid immunity, generated through a combination of vaccination and infection. Concerns have been raised that omicron breakthrough infections in triple-vaccinated individuals result in poor induction of omicron-specific immunity, and that prior SARS-CoV-2 infection is associated with immune dampening. Taking a broad and comprehensive approach, we characterize mucosal and blood immunity to spike and non-spike antigens following BA.1/BA.2 infections in triple mRNA-vaccinated individuals, with and without prior SARS-CoV-2 infection. We find that most individuals increase BA.1/BA.2/BA.5-specific neutralizing antibodies following infection, but confirm that the magnitude of increase and post-omicron titres are higher in the infection-naive. In contrast, significant increases in nasal responses, including neutralizing activity against BA.5 spike, are seen regardless of infection history. Spike-specific T cells increase only in infection-naive vaccinees; however, post-omicron T cell responses are significantly higher in the previously-infected, who display a maximally induced response with a highly cytotoxic CD8+ phenotype following their 3rd mRNA vaccine dose. Responses to non-spike antigens increase significantly regardless of prior infection status. These findings suggest that hybrid immunity induced by omicron breakthrough infections is characterized by significant immune enhancement that can help protect against future omicron variants.

U2 - 10.1038/s41467-023-40592-4

DO - 10.1038/s41467-023-40592-4

M3 - Article

SN - 2041-1723

VL - 14

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 5065

ER -

Omicron infection following vaccination enhances a broad spectrum of immune responses dependent on infection history

Abstract

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