Strong peak immunogenicity but rapid antibody waning following third vaccine dose in older residents of care homes

Crick COVID Immunity Pipeline

doi:10.1038/s43587-022-00328-3

Strong peak immunogenicity but rapid antibody waning following third vaccine dose in older residents of care homes

Crick COVID Immunity Pipeline

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Abstract

Third-dose coronavirus disease 2019 vaccines are being deployed widely but their efficacy has not been assessed adequately in vulnerable older people who exhibit suboptimal responses after primary vaccination series. This observational study, which was carried out by the VIVALDI study based in England, looked at spike-specific immune responses in 341 staff and residents in long-term care facilities who received an mRNA vaccine following dual primary series vaccination with BNT162b2 or ChAdOx1. Third-dose vaccination strongly increased antibody responses with preferential relative enhancement in older people and was required to elicit neutralization of Omicron. Cellular immune responses were also enhanced with strong cross-reactive recognition of Omicron. However, antibody titers fell 21-78% within 100 d after vaccine and 27% of participants developed a breakthrough Omicron infection. These findings reveal strong immunogenicity of a third vaccine in one of the most vulnerable population groups and endorse an approach for widespread delivery across this population. Ongoing assessment will be required to determine the stability of immune protection.

Original language	English
Pages (from-to)	93-104
Number of pages	12
Journal	Nature Aging
Volume	3
Issue number	1
DOIs	https://doi.org/10.1038/s43587-022-00328-3
Publication status	Published - 20 Jan 2023

Bibliographical note

Acknowledgements:
The authors would like to thank the staff and residents in the LTCFs that participated in this study, and Mark Marshall at NHS England who pseudonymised the electronic health records. This research was funded in whole, or in part, by the Wellcome Trust [CC2230, CC2087]. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. This work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (CC2230, CC2087), the UK Medical Research Council (CC2230, CC2087), and the Wellcome Trust (CC2230, CC2087); and the Department of Health and Social Care. This report is independent research funded by the Department of Health and Social Care (COVID-19 surveillance studies). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We thank Prof. Wendy Barclay of Imperial College and the wider Genotype to Phenotype consortium for the Delta strain used in this study, and Max Whiteley and Thushan I de Silva at The University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust for providing source material. We thank Prof. Gavin Screaton of the University of Oxford for the Omicron strain used in this study.

Copyright:
© 2023. The Author(s).

Keywords

Humans
Aged
BNT162 Vaccine
COVID-19/prevention & control
Antibodies
Vaccines
COVID-19 Vaccines
Breakthrough Infections

UN SDGs

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

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10.1038/s43587-022-00328-3Licence: Creative Commons: Attribution (CC BY)

TutG2023StrongFinal published version, 6.03 MBLicence: Creative Commons: Attribution (CC BY)

Cite this

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title = "Strong peak immunogenicity but rapid antibody waning following third vaccine dose in older residents of care homes",

abstract = "Third-dose coronavirus disease 2019 vaccines are being deployed widely but their efficacy has not been assessed adequately in vulnerable older people who exhibit suboptimal responses after primary vaccination series. This observational study, which was carried out by the VIVALDI study based in England, looked at spike-specific immune responses in 341 staff and residents in long-term care facilities who received an mRNA vaccine following dual primary series vaccination with BNT162b2 or ChAdOx1. Third-dose vaccination strongly increased antibody responses with preferential relative enhancement in older people and was required to elicit neutralization of Omicron. Cellular immune responses were also enhanced with strong cross-reactive recognition of Omicron. However, antibody titers fell 21-78% within 100 d after vaccine and 27% of participants developed a breakthrough Omicron infection. These findings reveal strong immunogenicity of a third vaccine in one of the most vulnerable population groups and endorse an approach for widespread delivery across this population. Ongoing assessment will be required to determine the stability of immune protection.",

keywords = "Humans, Aged, BNT162 Vaccine, COVID-19/prevention & control, Antibodies, Vaccines, COVID-19 Vaccines, Breakthrough Infections",

author = "{Crick COVID Immunity Pipeline} and Gokhan Tut and Tara Lancaster and Maria Krutikov and Panagiota Sylla and David Bone and Eliska Spalkova and Christopher Bentley and Umayr Amin and Azar Jadir and Samuel Hulme and Nayandeep Kaur and Elif Tut and Rachel Bruton and Wu, {Mary Y} and Ruth Harvey and Carr, {Edward J} and Rupert Beale and Oliver Stirrup and Madhumita Shrotri and Borscha Azmi and Christopher Fuller and Verity Baynton and Aidan Irwin-Singer and Andrew Hayward and Andrew Copas and Laura Shallcross and Paul Moss",

note = "Acknowledgements: The authors would like to thank the staff and residents in the LTCFs that participated in this study, and Mark Marshall at NHS England who pseudonymised the electronic health records. This research was funded in whole, or in part, by the Wellcome Trust [CC2230, CC2087]. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. This work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (CC2230, CC2087), the UK Medical Research Council (CC2230, CC2087), and the Wellcome Trust (CC2230, CC2087); and the Department of Health and Social Care. This report is independent research funded by the Department of Health and Social Care (COVID-19 surveillance studies). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We thank Prof. Wendy Barclay of Imperial College and the wider Genotype to Phenotype consortium for the Delta strain used in this study, and Max Whiteley and Thushan I de Silva at The University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust for providing source material. We thank Prof. Gavin Screaton of the University of Oxford for the Omicron strain used in this study. Copyright: {\textcopyright} 2023. The Author(s).",

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doi = "10.1038/s43587-022-00328-3",

language = "English",

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T1 - Strong peak immunogenicity but rapid antibody waning following third vaccine dose in older residents of care homes

AU - Crick COVID Immunity Pipeline

AU - Tut, Gokhan

AU - Lancaster, Tara

AU - Krutikov, Maria

AU - Sylla, Panagiota

AU - Bone, David

AU - Spalkova, Eliska

AU - Bentley, Christopher

AU - Amin, Umayr

AU - Jadir, Azar

AU - Hulme, Samuel

AU - Kaur, Nayandeep

AU - Tut, Elif

AU - Bruton, Rachel

AU - Wu, Mary Y

AU - Harvey, Ruth

AU - Carr, Edward J

AU - Beale, Rupert

AU - Stirrup, Oliver

AU - Shrotri, Madhumita

AU - Azmi, Borscha

AU - Fuller, Christopher

AU - Baynton, Verity

AU - Irwin-Singer, Aidan

AU - Hayward, Andrew

AU - Copas, Andrew

AU - Shallcross, Laura

AU - Moss, Paul

N1 - Acknowledgements: The authors would like to thank the staff and residents in the LTCFs that participated in this study, and Mark Marshall at NHS England who pseudonymised the electronic health records. This research was funded in whole, or in part, by the Wellcome Trust [CC2230, CC2087]. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. This work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (CC2230, CC2087), the UK Medical Research Council (CC2230, CC2087), and the Wellcome Trust (CC2230, CC2087); and the Department of Health and Social Care. This report is independent research funded by the Department of Health and Social Care (COVID-19 surveillance studies). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We thank Prof. Wendy Barclay of Imperial College and the wider Genotype to Phenotype consortium for the Delta strain used in this study, and Max Whiteley and Thushan I de Silva at The University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust for providing source material. We thank Prof. Gavin Screaton of the University of Oxford for the Omicron strain used in this study. Copyright: © 2023. The Author(s).

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Y1 - 2023/1/20

N2 - Third-dose coronavirus disease 2019 vaccines are being deployed widely but their efficacy has not been assessed adequately in vulnerable older people who exhibit suboptimal responses after primary vaccination series. This observational study, which was carried out by the VIVALDI study based in England, looked at spike-specific immune responses in 341 staff and residents in long-term care facilities who received an mRNA vaccine following dual primary series vaccination with BNT162b2 or ChAdOx1. Third-dose vaccination strongly increased antibody responses with preferential relative enhancement in older people and was required to elicit neutralization of Omicron. Cellular immune responses were also enhanced with strong cross-reactive recognition of Omicron. However, antibody titers fell 21-78% within 100 d after vaccine and 27% of participants developed a breakthrough Omicron infection. These findings reveal strong immunogenicity of a third vaccine in one of the most vulnerable population groups and endorse an approach for widespread delivery across this population. Ongoing assessment will be required to determine the stability of immune protection.

AB - Third-dose coronavirus disease 2019 vaccines are being deployed widely but their efficacy has not been assessed adequately in vulnerable older people who exhibit suboptimal responses after primary vaccination series. This observational study, which was carried out by the VIVALDI study based in England, looked at spike-specific immune responses in 341 staff and residents in long-term care facilities who received an mRNA vaccine following dual primary series vaccination with BNT162b2 or ChAdOx1. Third-dose vaccination strongly increased antibody responses with preferential relative enhancement in older people and was required to elicit neutralization of Omicron. Cellular immune responses were also enhanced with strong cross-reactive recognition of Omicron. However, antibody titers fell 21-78% within 100 d after vaccine and 27% of participants developed a breakthrough Omicron infection. These findings reveal strong immunogenicity of a third vaccine in one of the most vulnerable population groups and endorse an approach for widespread delivery across this population. Ongoing assessment will be required to determine the stability of immune protection.

KW - Humans

KW - Aged

KW - BNT162 Vaccine

KW - COVID-19/prevention & control

KW - Antibodies

KW - Vaccines

KW - COVID-19 Vaccines

KW - Breakthrough Infections

U2 - 10.1038/s43587-022-00328-3

DO - 10.1038/s43587-022-00328-3

M3 - Article

C2 - 37118525

SN - 2662-8465

VL - 3

SP - 93

EP - 104

JO - Nature Aging

JF - Nature Aging

IS - 1

ER -

Strong peak immunogenicity but rapid antibody waning following third vaccine dose in older residents of care homes

Abstract

Bibliographical note

Keywords

UN SDGs

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