Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three month analyses of the COV-BOOST trial.

the COV-BOOST study group; Xinxue Liu; Alasdair P.S. Munro; Shuo Feng; Leila Janani; Parvinder K. Aley; Gavin Babbage; David Baxter; Marcin Bula; Katrina Cathie; Krishna Chatterjee; Wanwisa Dejnirattisai; Kate Dodd; Yvanne Enever; Ehsaan Qureshi; Anna L. Goodman; Christopher A. Green; Linda Harndahl; John Haughney; Alexander Hicks; Agatha A. van der Klaauw; Jonathan Kwok; Vincenzo Libri; Martin J. Llewelyn; Alastair C. McGregor; Angela M. Minassian; Patrick Moore; Mehmood Mughal; Yama F. Mujadidi; Kyra Holliday; Orod Osanlou; Rostam Osanlou; Daniel R. Owens; Mihaela Pacurar; Adrian Palfreeman; Daniel Pan; Tommy Rampling; Karen Regan; Stephen Saich; Teona Serafimova; Dinesh Saralaya; Gavin R. Screaton; Sunil Sharma; Ray Sheridan; Ann Sturdy; Piyada Supasa; Sue Charlton; Bassam Hallis; Mary Ramsay; Nick Andrews; Jonathan S. Nguyen-Van-Tam; Emma C. Thomson; Shirley Todd; Christopher Twelves; Robert C. Read; Victoria Cornelius; Matthew D. Snape; Saul N. Faust

doi:10.1016/j.jinf.2022.04.018

Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three month analyses of the COV-BOOST trial.

the COV-BOOST study group, Xinxue Liu, Alasdair P.S. Munro, Shuo Feng, Leila Janani, Parvinder K. Aley, Gavin Babbage, David Baxter, Marcin Bula, Katrina Cathie, Krishna Chatterjee, Wanwisa Dejnirattisai, Kate Dodd, Yvanne Enever, Ehsaan Qureshi, Anna L. Goodman, Christopher A. Green, Linda Harndahl, John Haughney, Alexander HicksAgatha A. van der Klaauw, Jonathan Kwok, Vincenzo Libri, Martin J. Llewelyn, Alastair C. McGregor, Angela M. Minassian, Patrick Moore, Mehmood Mughal, Yama F. Mujadidi, Kyra Holliday, Orod Osanlou, Rostam Osanlou, Daniel R. Owens, Mihaela Pacurar, Adrian Palfreeman, Daniel Pan, Tommy Rampling, Karen Regan, Stephen Saich, Teona Serafimova, Dinesh Saralaya, Gavin R. Screaton, Sunil Sharma, Ray Sheridan, Ann Sturdy, Piyada Supasa, Sue Charlton, Bassam Hallis, Mary Ramsay, Nick Andrews, Jonathan S. Nguyen-Van-Tam, Emma C. Thomson, Shirley Todd, Christopher Twelves, Robert C. Read, Victoria Cornelius, Matthew D. Snape, Saul N. Faust

UK Health Security Agency

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

46 Citations (Scopus)

7 Downloads (Pure)

Abstract

Objectives: To evaluate the persistence of immunogenicity three months after third dose boosters.

Methods: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose. The analysis was conducted using all randomised participants who were SARS-CoV-2 naïve during the study.

Results: Amongst the 2883 participants randomised, there were 2422 SARS-CoV-2 naïve participants until D84 visit included in the analysis with median age of 70 (IQR: 30–94) years. In the participants who had two initial doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd), schedules using mRNA vaccines as third dose have the highest anti-spike IgG at D84 (e.g. geometric mean concentration of 8674 ELU/ml (95% CI: 7461–10,085) following ChAd/ChAd/BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT)). However, in people who had two initial doses of BNT there was no significant difference at D84 in people given ChAd versus BNT (geometric mean ratio (GMR) of 0.95 (95%CI: 0.78, 1.15). Also, people given Ad26.COV2.S (Janssen; hereafter referred to as Ad26) as a third dose had significantly higher anti-spike IgG at D84 than BNT (GMR of 1.20, 95%CI: 1.01,1.43). Responses at D84 between people who received BNT (15 μg) or BNT (30 μg) after ChAd/ChAd or BNT/BNT were similar, with anti-spike IgG GMRs of half-BNT (15 μg) versus BNT (30 μg) ranging between 0.74–0.86. The decay rate of cellular responses were similar between all the vaccine schedules and doses.

Conclusions: 84 days after a third dose of COVID-19 vaccine the decay rates of humoral response were different between vaccines. Adenoviral vector vaccine anti-spike IgG concentrations at D84 following BNT/BNT initial doses were similar to or even higher than for a three dose (BNT/BNT/BNT) schedule. Half dose BNT immune responses were similar to full dose responses. While high antibody tires are desirable in situations of high transmission of new variants of concern, the maintenance of immune responses that confer long-lasting protection against severe disease or death is also of critical importance. Policymakers may also consider adenoviral vector, fractional dose of mRNA, or other non-mRNA vaccines as third doses.

Original language	English
Pages (from-to)	795-813
Number of pages	19
Journal	Journal of Infection
Volume	84
Issue number	6
Early online date	9 Apr 2022
DOIs	https://doi.org/10.1016/j.jinf.2022.04.018
Publication status	Published - Jun 2022

Bibliographical note

Funding Information: The study is funded by the UK Government through the National Institute for Health Research (NIHR) and the Vaccine Task Force (VTF). The study Sponsor is University Hospital Southampton NHS Foundation Trust, Southampton, UK. ChAd, BNT and m1273 used in this study were supplied by the UK Health Security Agency (previously Public Health England). NVX, VLA, Ad26 and CVn were supplied by the manufacturers, without charge. The research is supported by the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, the NIHR Clinical Research Facilities and NIHR Clinical Research Network and the NIHR funded National Immunisation Schedule Evaluation Consortium (NISEC). SNF and MDS are NIHR Senior Investigators. KC is a Wellcome Trust Investigator (210755/Z/18/Z) and NIHR Senior Investigator Emeritus. GRS and TL received funding from the Chinese Academy of Medical Science (CAMS) Oxford Institute (COI). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.
KC acts on behalf of University Hospital Southampton as an investigator on studies funded or sponsored by vaccine manufacturers including AstraZeneca, GlaxoSmithKline, Janssen, Medimmune, Merck, Pfizer, Sanofi and Valneva. She receives no personal financial payment for this work. SNF acts on behalf of University Hospital Southampton NHS Foundation Trust as an Investigator
and/or providing consultative advice on clinical trials and studies of COVID-19 and other vaccines funded or sponsored by vac-cine manufacturers including Janssen, Pfizer, AstraZeneca, GlaxoSmithKline, Novavax, Seqirus, Sanofi, Medimmune, Merck and Valneva vaccines and antimicrobials. He receives no personal financial payment for this work. ALG is named as an inventor on a patent
covering use of a particular promoter construct that is often used in ChAdOx1-vectored vaccines and is incorporated in the ChAdOx1 nCoV-19 vaccine. ALG may benefit from royalty income paid to the University of Oxford from sales of this vaccine by AstraZeneca and its sublicensees under the University’s revenue sharing policy. JH has received payments for presentations for AstraZeneca,
Boehringer Ingelheim, Chiesi, Ciple & Teva. VL acts on behalf of University College London Hospitals NHS Foundation Trust as an Investigator on clinical trials of COVID-19 vaccines funded or sponsored by vaccine manufacturers including Pfizer, AstraZeneca and Valneva. He receives no personal financial payment for this work. PM acts on behalf of University Hospital Southampton NHS Foundation Trust and The Adam Practice as an investigator on studies funded or sponsored by vaccine manufacturers including AstraZeneca, GlaxoSmithKline, Novavax, Medicago and Sanofi. He received no personal financial payment for this work. JSN-V-T is seconded to the Department of Health and Social Care, England until 31st March 2022. MR has provided post marketing surveillance reports on vaccines for Pfizer and GSK for which a cost recover charge is made. MDS acts on behalf of the University of Oxford as an investigator on studies funded or sponsored by vaccine manufacturers including AstraZeneca, GlaxoSmithKline, Pfizer, Novavax. Janssen, Medimmune and MCM vaccines. He received no personal
financial payment for this work.

Open Access: This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/)

Publisher Copyright: © 2022 The Author(s). Published by Elsevier Ltd on behalf of The British Infection Association.

Citation: Xinxue Liu, Alasdair P S Munro, Shuo Feng, Leila Janani, Parvinder K Aley, Gavin Babbage, David Baxter, Marcin Bula, Katrina Cathie, Krishna Chatterjee, Wanwisa Dejnirattisai, Kate Dodd, Yvanne Enever, Ehsaan Qureshi, Anna L. Goodman, Christopher A Green, Linda Harndahl, John Haughney, Alexander Hicks, Agatha A. van der Klaauw, Jonathan Kwok, Vincenzo Libri, Martin J Llewelyn, Alastair C McGregor, Angela M. Minassian, Patrick Moore, Mehmood Mughal, Yama F Mujadidi, Kyra Holliday, Orod Osanlou, Rostam Osanlou, Daniel R Owens, Mihaela Pacurar, Adrian Palfreeman, Daniel Pan, Tommy Rampling, Karen Regan, Stephen Saich, Teona Serafimova, Dinesh Saralaya, Gavin R Screaton, Sunil Sharma, Ray Sheridan, Ann Sturdy, Piyada Supasa, Emma C Thomson, Shirley Todd, Chris Twelves, Robert C. Read, Sue Charlton, Bassam Hallis, Mary Ramsay, Nick Andrews, Teresa Lambe, Jonathan S Nguyen-Van-Tam, Victoria Cornelius, Matthew D Snape, Saul N Faust, Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three month analyses of the COV-BOOST trial.,
Journal of Infection, Volume 84, Issue 6, 2022, Pages 795-813, ISSN 0163-4453,
https://doi.org/10.1016/j.jinf.2022.04.018 (https://www.sciencedirect.com/science/article/pii/S0163445322002006)

DOI: https://doi.org/10.1016/j.jinf.2022.04.018

Keywords

COVID-19 vaccine
Fractional dose
Heterologous boost
Homologous boost
Immunogenicity
Persistence
Third dose

UN SDGs

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

Access to Document

10.1016/j.jinf.2022.04.018Licence: CC BY

Liu2022PersistenceOfImmunogenicityAfterSevenCOVID-19VaccinesGivenAsThirdDoseBoostersFollowingTwoDosesJInfectFinal published version, 6.02 MBLicence: CC BY

Cite this

the COV-BOOST study group, Liu, X., Munro, A. P. S., Feng, S., Janani, L., Aley, P. K., Babbage, G., Baxter, D., Bula, M., Cathie, K., Chatterjee, K., Dejnirattisai, W., Dodd, K., Enever, Y., Qureshi, E., Goodman, A. L., Green, C. A., Harndahl, L., Haughney, J., ... Faust, S. N. (2022). Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three month analyses of the COV-BOOST trial. Journal of Infection, 84(6), 795-813. https://doi.org/10.1016/j.jinf.2022.04.018

@article{a8bca99f17a147a4a8b3c1e6f6a02688,

title = "Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three month analyses of the COV-BOOST trial.",

abstract = "Objectives: To evaluate the persistence of immunogenicity three months after third dose boosters. Methods: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose. The analysis was conducted using all randomised participants who were SARS-CoV-2 na{\"i}ve during the study. Results: Amongst the 2883 participants randomised, there were 2422 SARS-CoV-2 na{\"i}ve participants until D84 visit included in the analysis with median age of 70 (IQR: 30–94) years. In the participants who had two initial doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd), schedules using mRNA vaccines as third dose have the highest anti-spike IgG at D84 (e.g. geometric mean concentration of 8674 ELU/ml (95% CI: 7461–10,085) following ChAd/ChAd/BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT)). However, in people who had two initial doses of BNT there was no significant difference at D84 in people given ChAd versus BNT (geometric mean ratio (GMR) of 0.95 (95%CI: 0.78, 1.15). Also, people given Ad26.COV2.S (Janssen; hereafter referred to as Ad26) as a third dose had significantly higher anti-spike IgG at D84 than BNT (GMR of 1.20, 95%CI: 1.01,1.43). Responses at D84 between people who received BNT (15 μg) or BNT (30 μg) after ChAd/ChAd or BNT/BNT were similar, with anti-spike IgG GMRs of half-BNT (15 μg) versus BNT (30 μg) ranging between 0.74–0.86. The decay rate of cellular responses were similar between all the vaccine schedules and doses. Conclusions: 84 days after a third dose of COVID-19 vaccine the decay rates of humoral response were different between vaccines. Adenoviral vector vaccine anti-spike IgG concentrations at D84 following BNT/BNT initial doses were similar to or even higher than for a three dose (BNT/BNT/BNT) schedule. Half dose BNT immune responses were similar to full dose responses. While high antibody tires are desirable in situations of high transmission of new variants of concern, the maintenance of immune responses that confer long-lasting protection against severe disease or death is also of critical importance. Policymakers may also consider adenoviral vector, fractional dose of mRNA, or other non-mRNA vaccines as third doses.",

keywords = "COVID-19 vaccine, Fractional dose, Heterologous boost, Homologous boost, Immunogenicity, Persistence, Third dose",

author = "{the COV-BOOST study group} and Xinxue Liu and Munro, {Alasdair P.S.} and Shuo Feng and Leila Janani and Aley, {Parvinder K.} and Gavin Babbage and David Baxter and Marcin Bula and Katrina Cathie and Krishna Chatterjee and Wanwisa Dejnirattisai and Kate Dodd and Yvanne Enever and Ehsaan Qureshi and Goodman, {Anna L.} and Green, {Christopher A.} and Linda Harndahl and John Haughney and Alexander Hicks and {van der Klaauw}, {Agatha A.} and Jonathan Kwok and Vincenzo Libri and Llewelyn, {Martin J.} and McGregor, {Alastair C.} and Minassian, {Angela M.} and Patrick Moore and Mehmood Mughal and Mujadidi, {Yama F.} and Kyra Holliday and Orod Osanlou and Rostam Osanlou and Owens, {Daniel R.} and Mihaela Pacurar and Adrian Palfreeman and Daniel Pan and Tommy Rampling and Karen Regan and Stephen Saich and Teona Serafimova and Dinesh Saralaya and Screaton, {Gavin R.} and Sunil Sharma and Ray Sheridan and Ann Sturdy and Piyada Supasa and Sue Charlton and Bassam Hallis and Mary Ramsay and Nick Andrews and Nguyen-Van-Tam, {Jonathan S.} and Thomson, {Emma C.} and Shirley Todd and Christopher Twelves and Read, {Robert C.} and Victoria Cornelius and Snape, {Matthew D.} and Faust, {Saul N.}",

note = "Funding Information: The study is funded by the UK Government through the National Institute for Health Research (NIHR) and the Vaccine Task Force (VTF). The study Sponsor is University Hospital Southampton NHS Foundation Trust, Southampton, UK. ChAd, BNT and m1273 used in this study were supplied by the UK Health Security Agency (previously Public Health England). NVX, VLA, Ad26 and CVn were supplied by the manufacturers, without charge. The research is supported by the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, the NIHR Clinical Research Facilities and NIHR Clinical Research Network and the NIHR funded National Immunisation Schedule Evaluation Consortium (NISEC). SNF and MDS are NIHR Senior Investigators. KC is a Wellcome Trust Investigator (210755/Z/18/Z) and NIHR Senior Investigator Emeritus. GRS and TL received funding from the Chinese Academy of Medical Science (CAMS) Oxford Institute (COI). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. KC acts on behalf of University Hospital Southampton as an investigator on studies funded or sponsored by vaccine manufacturers including AstraZeneca, GlaxoSmithKline, Janssen, Medimmune, Merck, Pfizer, Sanofi and Valneva. She receives no personal financial payment for this work. SNF acts on behalf of University Hospital Southampton NHS Foundation Trust as an Investigator and/or providing consultative advice on clinical trials and studies of COVID-19 and other vaccines funded or sponsored by vac-cine manufacturers including Janssen, Pfizer, AstraZeneca, GlaxoSmithKline, Novavax, Seqirus, Sanofi, Medimmune, Merck and Valneva vaccines and antimicrobials. He receives no personal financial payment for this work. ALG is named as an inventor on a patent covering use of a particular promoter construct that is often used in ChAdOx1-vectored vaccines and is incorporated in the ChAdOx1 nCoV-19 vaccine. ALG may benefit from royalty income paid to the University of Oxford from sales of this vaccine by AstraZeneca and its sublicensees under the University{\textquoteright}s revenue sharing policy. JH has received payments for presentations for AstraZeneca, Boehringer Ingelheim, Chiesi, Ciple & Teva. VL acts on behalf of University College London Hospitals NHS Foundation Trust as an Investigator on clinical trials of COVID-19 vaccines funded or sponsored by vaccine manufacturers including Pfizer, AstraZeneca and Valneva. He receives no personal financial payment for this work. PM acts on behalf of University Hospital Southampton NHS Foundation Trust and The Adam Practice as an investigator on studies funded or sponsored by vaccine manufacturers including AstraZeneca, GlaxoSmithKline, Novavax, Medicago and Sanofi. He received no personal financial payment for this work. JSN-V-T is seconded to the Department of Health and Social Care, England until 31st March 2022. MR has provided post marketing surveillance reports on vaccines for Pfizer and GSK for which a cost recover charge is made. MDS acts on behalf of the University of Oxford as an investigator on studies funded or sponsored by vaccine manufacturers including AstraZeneca, GlaxoSmithKline, Pfizer, Novavax. Janssen, Medimmune and MCM vaccines. He received no personal financial payment for this work. Open Access: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) Publisher Copyright: {\textcopyright} 2022 The Author(s). Published by Elsevier Ltd on behalf of The British Infection Association. Citation: Xinxue Liu, Alasdair P S Munro, Shuo Feng, Leila Janani, Parvinder K Aley, Gavin Babbage, David Baxter, Marcin Bula, Katrina Cathie, Krishna Chatterjee, Wanwisa Dejnirattisai, Kate Dodd, Yvanne Enever, Ehsaan Qureshi, Anna L. Goodman, Christopher A Green, Linda Harndahl, John Haughney, Alexander Hicks, Agatha A. van der Klaauw, Jonathan Kwok, Vincenzo Libri, Martin J Llewelyn, Alastair C McGregor, Angela M. Minassian, Patrick Moore, Mehmood Mughal, Yama F Mujadidi, Kyra Holliday, Orod Osanlou, Rostam Osanlou, Daniel R Owens, Mihaela Pacurar, Adrian Palfreeman, Daniel Pan, Tommy Rampling, Karen Regan, Stephen Saich, Teona Serafimova, Dinesh Saralaya, Gavin R Screaton, Sunil Sharma, Ray Sheridan, Ann Sturdy, Piyada Supasa, Emma C Thomson, Shirley Todd, Chris Twelves, Robert C. Read, Sue Charlton, Bassam Hallis, Mary Ramsay, Nick Andrews, Teresa Lambe, Jonathan S Nguyen-Van-Tam, Victoria Cornelius, Matthew D Snape, Saul N Faust, Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three month analyses of the COV-BOOST trial., Journal of Infection, Volume 84, Issue 6, 2022, Pages 795-813, ISSN 0163-4453, https://doi.org/10.1016/j.jinf.2022.04.018 (https://www.sciencedirect.com/science/article/pii/S0163445322002006) DOI: https://doi.org/10.1016/j.jinf.2022.04.018",

year = "2022",

month = jun,

doi = "10.1016/j.jinf.2022.04.018",

language = "English",

volume = "84",

pages = "795--813",

journal = "Journal of Infection",

issn = "0163-4453",

publisher = "W.B. Saunders Ltd",

number = "6",

}

the COV-BOOST study group, Liu, X, Munro, APS, Feng, S, Janani, L, Aley, PK, Babbage, G, Baxter, D, Bula, M, Cathie, K, Chatterjee, K, Dejnirattisai, W, Dodd, K, Enever, Y, Qureshi, E, Goodman, AL, Green, CA, Harndahl, L, Haughney, J, Hicks, A, van der Klaauw, AA, Kwok, J, Libri, V, Llewelyn, MJ, McGregor, AC, Minassian, AM, Moore, P, Mughal, M, Mujadidi, YF, Holliday, K, Osanlou, O, Osanlou, R, Owens, DR, Pacurar, M, Palfreeman, A, Pan, D, Rampling, T, Regan, K, Saich, S, Serafimova, T, Saralaya, D, Screaton, GR, Sharma, S, Sheridan, R, Sturdy, A, Supasa, P, Charlton, S , Hallis, B , Ramsay, M , Andrews, N, Nguyen-Van-Tam, JS, Thomson, EC, Todd, S, Twelves, C, Read, RC, Cornelius, V, Snape, MD & Faust, SN 2022, 'Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three month analyses of the COV-BOOST trial.', Journal of Infection, vol. 84, no. 6, pp. 795-813. https://doi.org/10.1016/j.jinf.2022.04.018

Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three month analyses of the COV-BOOST trial. / the COV-BOOST study group; Liu, Xinxue; Munro, Alasdair P.S. et al.
In: Journal of Infection, Vol. 84, No. 6, 06.2022, p. 795-813.

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

TY - JOUR

T1 - Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK

T2 - Three month analyses of the COV-BOOST trial.

AU - the COV-BOOST study group

AU - Liu, Xinxue

AU - Munro, Alasdair P.S.

AU - Feng, Shuo

AU - Janani, Leila

AU - Aley, Parvinder K.

AU - Babbage, Gavin

AU - Baxter, David

AU - Bula, Marcin

AU - Cathie, Katrina

AU - Chatterjee, Krishna

AU - Dejnirattisai, Wanwisa

AU - Dodd, Kate

AU - Enever, Yvanne

AU - Qureshi, Ehsaan

AU - Goodman, Anna L.

AU - Green, Christopher A.

AU - Harndahl, Linda

AU - Haughney, John

AU - Hicks, Alexander

AU - van der Klaauw, Agatha A.

AU - Kwok, Jonathan

AU - Libri, Vincenzo

AU - Llewelyn, Martin J.

AU - McGregor, Alastair C.

AU - Minassian, Angela M.

AU - Moore, Patrick

AU - Mughal, Mehmood

AU - Mujadidi, Yama F.

AU - Holliday, Kyra

AU - Osanlou, Orod

AU - Osanlou, Rostam

AU - Owens, Daniel R.

AU - Pacurar, Mihaela

AU - Palfreeman, Adrian

AU - Pan, Daniel

AU - Rampling, Tommy

AU - Regan, Karen

AU - Saich, Stephen

AU - Serafimova, Teona

AU - Saralaya, Dinesh

AU - Screaton, Gavin R.

AU - Sharma, Sunil

AU - Sheridan, Ray

AU - Sturdy, Ann

AU - Supasa, Piyada

AU - Charlton, Sue

AU - Hallis, Bassam

AU - Ramsay, Mary

AU - Andrews, Nick

AU - Nguyen-Van-Tam, Jonathan S.

AU - Thomson, Emma C.

AU - Todd, Shirley

AU - Twelves, Christopher

AU - Read, Robert C.

AU - Cornelius, Victoria

AU - Snape, Matthew D.

AU - Faust, Saul N.

N1 - Funding Information: The study is funded by the UK Government through the National Institute for Health Research (NIHR) and the Vaccine Task Force (VTF). The study Sponsor is University Hospital Southampton NHS Foundation Trust, Southampton, UK. ChAd, BNT and m1273 used in this study were supplied by the UK Health Security Agency (previously Public Health England). NVX, VLA, Ad26 and CVn were supplied by the manufacturers, without charge. The research is supported by the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, the NIHR Clinical Research Facilities and NIHR Clinical Research Network and the NIHR funded National Immunisation Schedule Evaluation Consortium (NISEC). SNF and MDS are NIHR Senior Investigators. KC is a Wellcome Trust Investigator (210755/Z/18/Z) and NIHR Senior Investigator Emeritus. GRS and TL received funding from the Chinese Academy of Medical Science (CAMS) Oxford Institute (COI). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. KC acts on behalf of University Hospital Southampton as an investigator on studies funded or sponsored by vaccine manufacturers including AstraZeneca, GlaxoSmithKline, Janssen, Medimmune, Merck, Pfizer, Sanofi and Valneva. She receives no personal financial payment for this work. SNF acts on behalf of University Hospital Southampton NHS Foundation Trust as an Investigator and/or providing consultative advice on clinical trials and studies of COVID-19 and other vaccines funded or sponsored by vac-cine manufacturers including Janssen, Pfizer, AstraZeneca, GlaxoSmithKline, Novavax, Seqirus, Sanofi, Medimmune, Merck and Valneva vaccines and antimicrobials. He receives no personal financial payment for this work. ALG is named as an inventor on a patent covering use of a particular promoter construct that is often used in ChAdOx1-vectored vaccines and is incorporated in the ChAdOx1 nCoV-19 vaccine. ALG may benefit from royalty income paid to the University of Oxford from sales of this vaccine by AstraZeneca and its sublicensees under the University’s revenue sharing policy. JH has received payments for presentations for AstraZeneca, Boehringer Ingelheim, Chiesi, Ciple & Teva. VL acts on behalf of University College London Hospitals NHS Foundation Trust as an Investigator on clinical trials of COVID-19 vaccines funded or sponsored by vaccine manufacturers including Pfizer, AstraZeneca and Valneva. He receives no personal financial payment for this work. PM acts on behalf of University Hospital Southampton NHS Foundation Trust and The Adam Practice as an investigator on studies funded or sponsored by vaccine manufacturers including AstraZeneca, GlaxoSmithKline, Novavax, Medicago and Sanofi. He received no personal financial payment for this work. JSN-V-T is seconded to the Department of Health and Social Care, England until 31st March 2022. MR has provided post marketing surveillance reports on vaccines for Pfizer and GSK for which a cost recover charge is made. MDS acts on behalf of the University of Oxford as an investigator on studies funded or sponsored by vaccine manufacturers including AstraZeneca, GlaxoSmithKline, Pfizer, Novavax. Janssen, Medimmune and MCM vaccines. He received no personal financial payment for this work. Open Access: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) Publisher Copyright: © 2022 The Author(s). Published by Elsevier Ltd on behalf of The British Infection Association. Citation: Xinxue Liu, Alasdair P S Munro, Shuo Feng, Leila Janani, Parvinder K Aley, Gavin Babbage, David Baxter, Marcin Bula, Katrina Cathie, Krishna Chatterjee, Wanwisa Dejnirattisai, Kate Dodd, Yvanne Enever, Ehsaan Qureshi, Anna L. Goodman, Christopher A Green, Linda Harndahl, John Haughney, Alexander Hicks, Agatha A. van der Klaauw, Jonathan Kwok, Vincenzo Libri, Martin J Llewelyn, Alastair C McGregor, Angela M. Minassian, Patrick Moore, Mehmood Mughal, Yama F Mujadidi, Kyra Holliday, Orod Osanlou, Rostam Osanlou, Daniel R Owens, Mihaela Pacurar, Adrian Palfreeman, Daniel Pan, Tommy Rampling, Karen Regan, Stephen Saich, Teona Serafimova, Dinesh Saralaya, Gavin R Screaton, Sunil Sharma, Ray Sheridan, Ann Sturdy, Piyada Supasa, Emma C Thomson, Shirley Todd, Chris Twelves, Robert C. Read, Sue Charlton, Bassam Hallis, Mary Ramsay, Nick Andrews, Teresa Lambe, Jonathan S Nguyen-Van-Tam, Victoria Cornelius, Matthew D Snape, Saul N Faust, Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three month analyses of the COV-BOOST trial., Journal of Infection, Volume 84, Issue 6, 2022, Pages 795-813, ISSN 0163-4453, https://doi.org/10.1016/j.jinf.2022.04.018 (https://www.sciencedirect.com/science/article/pii/S0163445322002006) DOI: https://doi.org/10.1016/j.jinf.2022.04.018

PY - 2022/6

Y1 - 2022/6

N2 - Objectives: To evaluate the persistence of immunogenicity three months after third dose boosters. Methods: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose. The analysis was conducted using all randomised participants who were SARS-CoV-2 naïve during the study. Results: Amongst the 2883 participants randomised, there were 2422 SARS-CoV-2 naïve participants until D84 visit included in the analysis with median age of 70 (IQR: 30–94) years. In the participants who had two initial doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd), schedules using mRNA vaccines as third dose have the highest anti-spike IgG at D84 (e.g. geometric mean concentration of 8674 ELU/ml (95% CI: 7461–10,085) following ChAd/ChAd/BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT)). However, in people who had two initial doses of BNT there was no significant difference at D84 in people given ChAd versus BNT (geometric mean ratio (GMR) of 0.95 (95%CI: 0.78, 1.15). Also, people given Ad26.COV2.S (Janssen; hereafter referred to as Ad26) as a third dose had significantly higher anti-spike IgG at D84 than BNT (GMR of 1.20, 95%CI: 1.01,1.43). Responses at D84 between people who received BNT (15 μg) or BNT (30 μg) after ChAd/ChAd or BNT/BNT were similar, with anti-spike IgG GMRs of half-BNT (15 μg) versus BNT (30 μg) ranging between 0.74–0.86. The decay rate of cellular responses were similar between all the vaccine schedules and doses. Conclusions: 84 days after a third dose of COVID-19 vaccine the decay rates of humoral response were different between vaccines. Adenoviral vector vaccine anti-spike IgG concentrations at D84 following BNT/BNT initial doses were similar to or even higher than for a three dose (BNT/BNT/BNT) schedule. Half dose BNT immune responses were similar to full dose responses. While high antibody tires are desirable in situations of high transmission of new variants of concern, the maintenance of immune responses that confer long-lasting protection against severe disease or death is also of critical importance. Policymakers may also consider adenoviral vector, fractional dose of mRNA, or other non-mRNA vaccines as third doses.

AB - Objectives: To evaluate the persistence of immunogenicity three months after third dose boosters. Methods: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose. The analysis was conducted using all randomised participants who were SARS-CoV-2 naïve during the study. Results: Amongst the 2883 participants randomised, there were 2422 SARS-CoV-2 naïve participants until D84 visit included in the analysis with median age of 70 (IQR: 30–94) years. In the participants who had two initial doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd), schedules using mRNA vaccines as third dose have the highest anti-spike IgG at D84 (e.g. geometric mean concentration of 8674 ELU/ml (95% CI: 7461–10,085) following ChAd/ChAd/BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT)). However, in people who had two initial doses of BNT there was no significant difference at D84 in people given ChAd versus BNT (geometric mean ratio (GMR) of 0.95 (95%CI: 0.78, 1.15). Also, people given Ad26.COV2.S (Janssen; hereafter referred to as Ad26) as a third dose had significantly higher anti-spike IgG at D84 than BNT (GMR of 1.20, 95%CI: 1.01,1.43). Responses at D84 between people who received BNT (15 μg) or BNT (30 μg) after ChAd/ChAd or BNT/BNT were similar, with anti-spike IgG GMRs of half-BNT (15 μg) versus BNT (30 μg) ranging between 0.74–0.86. The decay rate of cellular responses were similar between all the vaccine schedules and doses. Conclusions: 84 days after a third dose of COVID-19 vaccine the decay rates of humoral response were different between vaccines. Adenoviral vector vaccine anti-spike IgG concentrations at D84 following BNT/BNT initial doses were similar to or even higher than for a three dose (BNT/BNT/BNT) schedule. Half dose BNT immune responses were similar to full dose responses. While high antibody tires are desirable in situations of high transmission of new variants of concern, the maintenance of immune responses that confer long-lasting protection against severe disease or death is also of critical importance. Policymakers may also consider adenoviral vector, fractional dose of mRNA, or other non-mRNA vaccines as third doses.

KW - COVID-19 vaccine

KW - Fractional dose

KW - Heterologous boost

KW - Homologous boost

KW - Immunogenicity

KW - Persistence

KW - Third dose

UR - http://www.scopus.com/inward/record.url?scp=85130794798&partnerID=8YFLogxK

U2 - 10.1016/j.jinf.2022.04.018

DO - 10.1016/j.jinf.2022.04.018

M3 - Article

C2 - 35405168

AN - SCOPUS:85130794798

SN - 0163-4453

VL - 84

SP - 795

EP - 813

JO - Journal of Infection

JF - Journal of Infection

IS - 6

ER -

Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK: Three month analyses of the COV-BOOST trial.

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