Antibody and cellular immune responses following dual COVID-19 vaccination within infection-naive residents of long-term care facilities: an observational cohort study

Gokhan Tut, Tara Lancaster, Panagiota Sylla, Megan S. Butler, Nayandeep Kaur, Eliska Spalkova, Christopher Bentley, Umayr Amin, Azar Jadir, Samuel Hulme, Morenike Ayodele, David Bone, Elif Tut, Rachel Bruton, Maria Krutikov, Rebecca Giddings, Madhumita Shrotri, Borscha Azmi, Christopher Fuller, Verity BayntonAidan Irwin-Singer, Andrew Hayward, Andrew Copas, Laura Shallcross, Paul Moss*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Background: Older age and frailty are risk factors for poor clinical outcomes following SARS-CoV-2 infection. As such, COVID-19 vaccination has been prioritised for individuals with these factors, but there is concern that immune responses might be impaired due to age-related immune dysregulation and comorbidity. We aimed to study humoral and cellular responses to COVID-19 vaccines in residents of long-term care facilities (LTCFs). 

Methods: In this observational cohort study, we assessed antibody and cellular immune responses following COVID-19 vaccination in members of staff and residents at 74 LTCFs across the UK. Staff and residents were eligible for inclusion if it was possible to link them to a pseudo-identifier in the COVID-19 datastore, if they had received two vaccine doses, and if they had given a blood sample 6 days after vaccination at the earliest. There were no comorbidity exclusion criteria. Participants were stratified by age (<65 years or ≥65 years) and infection status (previous SARS-CoV-2 infection [infection-primed group] or SARS-CoV-2 naive [infection-naive group]). Anticoagulated edetic acid (EDTA) blood samples were assessed and humoral and cellular responses were quantified. 

Findings: Between Dec 11, 2020, and June 27, 2021, blood samples were taken from 220 people younger than 65 years (median age 51 years [IQR 39–61]; 103 [47%] had previously had a SARS-CoV-2 infection) and 268 people aged 65 years or older of LTCFs (median age 87 years [80–92]; 144 [43%] had a previous SARS-CoV-2 infection). Samples were taken a median of 82 days (IQR 72–100) after the second vaccination. Antibody responses following dual vaccination were strong and equivalent between participants younger then 65 years and those aged 65 years and older in the infection-primed group (median 125 285 Au/mL [1128 BAU/mL] for <65 year olds vs 157 979 Au/mL [1423 BAU/mL] for ≥65 year olds; p=0·47). The antibody response was reduced by 2·4-times (467 BAU/mL; p≤0·0001) in infection-naive people younger than 65 years and 8·1-times (174 BAU/mL; p≤0·0001) in infection-naive residents compared with their infection-primed counterparts. Antibody response was 2·6-times lower in infection-naive residents than in infection-naive people younger than 65 years (p=0·0006). Impaired neutralisation of delta (1.617.2) variant spike binding was also apparent in infection-naive people younger than 65 years and in those aged 65 years and older. Spike-specific T-cell responses were also significantly enhanced in the infection-primed group. Infection-naive people aged 65 years and older (203 SFU per million [IQR 89–374]) had a 52% lower T-cell response compared with infection-naive people younger than 65 years (85 SFU per million [30–206]; p≤0·0001). Post-vaccine spike-specific CD4 T-cell responses displayed single or dual production of IFN-γ and IL-2 were similar across infection status groups, whereas the infection-primed group had an extended functional profile with TNFα and CXCL10 production. 

Interpretation: These data reveal suboptimal post-vaccine immune responses within infection-naive residents of LTCFs, and they suggest the need for optimisation of immune protection through the use of booster vaccination. 

Funding: UK Government Department of Health and Social Care.

Original languageEnglish
Pages (from-to)e461-e469
JournalThe Lancet Healthy Longevity
Volume3
Issue number7
DOIs
Publication statusPublished - 4 Jul 2022

Bibliographical note

Funding Information: LS reports grants from the Department of Health and Social Care during the study and is a member of the Social Care Working Group, which reports to the Scientific Advisory Group for Emergencies. AH is a member of the New and Emerging Respiratory Virus Threats Advisory Group at the Department of Health. All other authors declare no competing interests.
The authors would like to thank the staff and residents in the long-term care facilities that participated in this study, and Mark Marshall at NHS England who pseudonymised the electronic health records. This report is independent research funded by the Department of Health and Social Care (COVID-19 surveillance studies).

Open Access: This is an Open Access article under the CC BY 4.0 license.

Publisher Copyright: © 2022 The Author(s). Published by Elsevier Ltd.

Citation: Gokhan Tut, Tara Lancaster, Panagiota Sylla, Megan S Butler, Nayandeep Kaur, Eliska Spalkova, Christopher Bentley, Umayr Amin, Azar Jadir, Samuel Hulme, Morenike Ayodele, David Bone, Elif Tut, Rachel Bruton, Maria Krutikov, Rebecca Giddings, Madhumita Shrotri, Borscha Azmi, Christopher Fuller, Verity Baynton, Aidan Irwin-Singer, Andrew Hayward, Andrew Copas, Laura Shallcross, Paul Moss, Antibody and cellular immune responses following dual COVID-19 vaccination within infection-naive residents of long-term care facilities: an observational cohort study, The Lancet Healthy Longevity, Volume 3, Issue 7, 2022, Pages e461-e469, ISSN 2666-7568,

DOI: https://doi.org/10.1016/S2666-7568(22)00118-0.

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