Boosting of Waned Humoral and Cellular Responses to SARS-CoV-2 Variants of Concern Among Patients with Cancer

Duncan R. McKenzie; Rosalind Graham; Thomas Lechmere; Clara Domingo-Vila; Thanussuyah Alaguthurai; Celeste Arman; Emily Pollock; Charalampos Gousis; Helen Kakkassery; Esme Carpenter; Ashwini Kurshan; Jennifer Vidler; Austin Kulasekararaj; Piers Patten; Bernard V. North; Timothy Tree; Katie J. Doores; Adrian C. Hayday; Sheeba Irshad

doi:10.1158/2767-9764.CRC-22-0298

Boosting of Waned Humoral and Cellular Responses to SARS-CoV-2 Variants of Concern Among Patients with Cancer

Duncan R. McKenzie, Rosalind Graham, Thomas Lechmere, Clara Domingo-Vila, Thanussuyah Alaguthurai, Celeste Arman, Emily Pollock, Charalampos Gousis, Helen Kakkassery, Esme Carpenter, Ashwini Kurshan, Jennifer Vidler, Austin Kulasekararaj, Piers Patten, Bernard V. North, Timothy Tree, Katie J. Doores, Adrian C. Hayday, Sheeba Irshad^*

^*Corresponding author for this work

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

2 Citations (Scopus)

Abstract

This study offers longitudinal insight into the impact of three SARS-CoV-2 vaccinations on humoral and cellular immunity in patients with solid cancers, patients with hematologic malignancies, and persons without cancer. For all cohorts, virus-neutralizing immunity was significantly depleted over a period of up to 9 months following the second vaccine dose, the one striking exception being IL2 production by SARS-CoV-2 antigen-specific T cells. Immunity was restored by the third vaccine dose, except in a substantial number of patients with hematologic malignancy, for whom both cancer type and treatment schedule were associated with nonresponse. Thus, whereas most patients with myelodysplastic syndrome were conspicuously good responders, some patients with other hematologic malignancies receiving cancer therapies within 2 weeks of vaccination showed no seroconversion despite three vaccine doses. Moreover, SARS-CoV-2 exposure during the course of the study neither prevented immunity waning, even in healthy controls, nor guaranteed vaccine responsiveness. These data offer real-world human immunologic insights that can inform health policy for patients with cancer. Significance: Global health policy reliant on SARS-CoV-2 vaccine effectiveness is underpinned by our understanding of the durability of protection offered by sequential vaccinations and the efficacy of boosting, especially in immunocompromised patient populations who might constitute virus reservoirs. Here, we have: (i) clarified in patients with cancer the degree of waning of antibodies, serum neutralization titres against parental virus and variants of concern, and T-cell responses; (ii) evaluated the immune response among patients with cancer to a third dose of COVID-19 vaccine; and (iii) provided safety data following the third dose of the BNT162b2 COVID-19 vaccine in patients with cancer.

Original language	English
Pages (from-to)	1449-1461
Number of pages	13
Journal	Cancer research communications
Volume	2
Issue number	11
DOIs	https://doi.org/10.1158/2767-9764.CRC-22-0298
Publication status	Published - 2022

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10.1158/2767-9764.CRC-22-0298

Cite this

McKenzie, D. R., Graham, R., Lechmere, T., Domingo-Vila, C., Alaguthurai, T., Arman, C., Pollock, E., Gousis, C., Kakkassery, H., Carpenter, E., Kurshan, A., Vidler, J., Kulasekararaj, A., Patten, P., North, B. V., Tree, T., Doores, K. J., Hayday, A. C., & Irshad, S. (2022). Boosting of Waned Humoral and Cellular Responses to SARS-CoV-2 Variants of Concern Among Patients with Cancer. Cancer research communications, 2(11), 1449-1461. https://doi.org/10.1158/2767-9764.CRC-22-0298

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title = "Boosting of Waned Humoral and Cellular Responses to SARS-CoV-2 Variants of Concern Among Patients with Cancer",

abstract = "This study offers longitudinal insight into the impact of three SARS-CoV-2 vaccinations on humoral and cellular immunity in patients with solid cancers, patients with hematologic malignancies, and persons without cancer. For all cohorts, virus-neutralizing immunity was significantly depleted over a period of up to 9 months following the second vaccine dose, the one striking exception being IL2 production by SARS-CoV-2 antigen-specific T cells. Immunity was restored by the third vaccine dose, except in a substantial number of patients with hematologic malignancy, for whom both cancer type and treatment schedule were associated with nonresponse. Thus, whereas most patients with myelodysplastic syndrome were conspicuously good responders, some patients with other hematologic malignancies receiving cancer therapies within 2 weeks of vaccination showed no seroconversion despite three vaccine doses. Moreover, SARS-CoV-2 exposure during the course of the study neither prevented immunity waning, even in healthy controls, nor guaranteed vaccine responsiveness. These data offer real-world human immunologic insights that can inform health policy for patients with cancer. Significance: Global health policy reliant on SARS-CoV-2 vaccine effectiveness is underpinned by our understanding of the durability of protection offered by sequential vaccinations and the efficacy of boosting, especially in immunocompromised patient populations who might constitute virus reservoirs. Here, we have: (i) clarified in patients with cancer the degree of waning of antibodies, serum neutralization titres against parental virus and variants of concern, and T-cell responses; (ii) evaluated the immune response among patients with cancer to a third dose of COVID-19 vaccine; and (iii) provided safety data following the third dose of the BNT162b2 COVID-19 vaccine in patients with cancer.",

author = "McKenzie, {Duncan R.} and Rosalind Graham and Thomas Lechmere and Clara Domingo-Vila and Thanussuyah Alaguthurai and Celeste Arman and Emily Pollock and Charalampos Gousis and Helen Kakkassery and Esme Carpenter and Ashwini Kurshan and Jennifer Vidler and Austin Kulasekararaj and Piers Patten and North, {Bernard V.} and Timothy Tree and Doores, {Katie J.} and Hayday, {Adrian C.} and Sheeba Irshad",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors.",

year = "2022",

doi = "10.1158/2767-9764.CRC-22-0298",

language = "English",

volume = "2",

pages = "1449--1461",

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McKenzie, DR, Graham, R, Lechmere, T, Domingo-Vila, C, Alaguthurai, T, Arman, C, Pollock, E, Gousis, C, Kakkassery, H, Carpenter, E, Kurshan, A, Vidler, J, Kulasekararaj, A, Patten, P, North, BV, Tree, T , Doores, KJ , Hayday, AC & Irshad, S 2022, 'Boosting of Waned Humoral and Cellular Responses to SARS-CoV-2 Variants of Concern Among Patients with Cancer', Cancer research communications, vol. 2, no. 11, pp. 1449-1461. https://doi.org/10.1158/2767-9764.CRC-22-0298

TY - JOUR

T1 - Boosting of Waned Humoral and Cellular Responses to SARS-CoV-2 Variants of Concern Among Patients with Cancer

AU - McKenzie, Duncan R.

AU - Graham, Rosalind

AU - Lechmere, Thomas

AU - Domingo-Vila, Clara

AU - Alaguthurai, Thanussuyah

AU - Arman, Celeste

AU - Pollock, Emily

AU - Gousis, Charalampos

AU - Kakkassery, Helen

AU - Carpenter, Esme

AU - Kurshan, Ashwini

AU - Vidler, Jennifer

AU - Kulasekararaj, Austin

AU - Patten, Piers

AU - North, Bernard V.

AU - Tree, Timothy

AU - Doores, Katie J.

AU - Hayday, Adrian C.

AU - Irshad, Sheeba

PY - 2022

Y1 - 2022

N2 - This study offers longitudinal insight into the impact of three SARS-CoV-2 vaccinations on humoral and cellular immunity in patients with solid cancers, patients with hematologic malignancies, and persons without cancer. For all cohorts, virus-neutralizing immunity was significantly depleted over a period of up to 9 months following the second vaccine dose, the one striking exception being IL2 production by SARS-CoV-2 antigen-specific T cells. Immunity was restored by the third vaccine dose, except in a substantial number of patients with hematologic malignancy, for whom both cancer type and treatment schedule were associated with nonresponse. Thus, whereas most patients with myelodysplastic syndrome were conspicuously good responders, some patients with other hematologic malignancies receiving cancer therapies within 2 weeks of vaccination showed no seroconversion despite three vaccine doses. Moreover, SARS-CoV-2 exposure during the course of the study neither prevented immunity waning, even in healthy controls, nor guaranteed vaccine responsiveness. These data offer real-world human immunologic insights that can inform health policy for patients with cancer. Significance: Global health policy reliant on SARS-CoV-2 vaccine effectiveness is underpinned by our understanding of the durability of protection offered by sequential vaccinations and the efficacy of boosting, especially in immunocompromised patient populations who might constitute virus reservoirs. Here, we have: (i) clarified in patients with cancer the degree of waning of antibodies, serum neutralization titres against parental virus and variants of concern, and T-cell responses; (ii) evaluated the immune response among patients with cancer to a third dose of COVID-19 vaccine; and (iii) provided safety data following the third dose of the BNT162b2 COVID-19 vaccine in patients with cancer.

AB - This study offers longitudinal insight into the impact of three SARS-CoV-2 vaccinations on humoral and cellular immunity in patients with solid cancers, patients with hematologic malignancies, and persons without cancer. For all cohorts, virus-neutralizing immunity was significantly depleted over a period of up to 9 months following the second vaccine dose, the one striking exception being IL2 production by SARS-CoV-2 antigen-specific T cells. Immunity was restored by the third vaccine dose, except in a substantial number of patients with hematologic malignancy, for whom both cancer type and treatment schedule were associated with nonresponse. Thus, whereas most patients with myelodysplastic syndrome were conspicuously good responders, some patients with other hematologic malignancies receiving cancer therapies within 2 weeks of vaccination showed no seroconversion despite three vaccine doses. Moreover, SARS-CoV-2 exposure during the course of the study neither prevented immunity waning, even in healthy controls, nor guaranteed vaccine responsiveness. These data offer real-world human immunologic insights that can inform health policy for patients with cancer. Significance: Global health policy reliant on SARS-CoV-2 vaccine effectiveness is underpinned by our understanding of the durability of protection offered by sequential vaccinations and the efficacy of boosting, especially in immunocompromised patient populations who might constitute virus reservoirs. Here, we have: (i) clarified in patients with cancer the degree of waning of antibodies, serum neutralization titres against parental virus and variants of concern, and T-cell responses; (ii) evaluated the immune response among patients with cancer to a third dose of COVID-19 vaccine; and (iii) provided safety data following the third dose of the BNT162b2 COVID-19 vaccine in patients with cancer.

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U2 - 10.1158/2767-9764.CRC-22-0298

DO - 10.1158/2767-9764.CRC-22-0298

M3 - Article

AN - SCOPUS:85180333537

SN - 2767-9764

VL - 2

SP - 1449

EP - 1461

JO - Cancer research communications

JF - Cancer research communications

IS - 11

ER -

Boosting of Waned Humoral and Cellular Responses to SARS-CoV-2 Variants of Concern Among Patients with Cancer

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