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

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; 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

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

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, Linda Harndahl, John Haughney, Alexander Hicks, Agatha A. van der Klaauw, Jonathan KwokVincenzo 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

School of Health Sciences

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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

Keywords

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

UN SDGs

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

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10.1016/j.jinf.2022.04.018

Persistence of immunogenicityFinal published version, 6.02 MBLicence: CC BY

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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., Harndahl, L., Haughney, J., Hicks, A., van der Klaauw, A. A., ... 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{be55739f71324869b6448065a1f27f3f,

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, Third dose, Heterologous boost, Homologous boost, Fractional dose, Immunogenicity, Persistence",

author = "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 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 Thomson, \{Emma C.\} and Shirley Todd and Chris Twelves and Read, \{Robert C.\} and Sue Charlton and Bassam Hallis and Mary Ramsay and Nick Andrews and Teresa Lambe and Nguyen-Van-Tam, \{Jonathan S.\} and Victoria Cornelius and Snape, \{Matthew D.\} and Faust, \{Saul N.\}",

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",

}

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, 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, Thomson, EC, Todd, S, Twelves, C, Read, RC, Charlton, S, Hallis, B, Ramsay, M, Andrews, N, Lambe, T, Nguyen-Van-Tam, JS, 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. / Liu, Xinxue; Munro, Alasdair P. S.; Feng, Shuo 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: Three month analyses of the COV-BOOST trial

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 - 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 - Thomson, Emma C.

AU - Todd, Shirley

AU - Twelves, Chris

AU - Read, Robert C.

AU - Charlton, Sue

AU - Hallis, Bassam

AU - Ramsay, Mary

AU - Andrews, Nick

AU - Lambe, Teresa

AU - Nguyen-Van-Tam, Jonathan S.

AU - Cornelius, Victoria

AU - Snape, Matthew D.

AU - Faust, Saul N.

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 - Third dose

KW - Heterologous boost

KW - Homologous boost

KW - Fractional dose

KW - Immunogenicity

KW - Persistence

U2 - 10.1016/j.jinf.2022.04.018

DO - 10.1016/j.jinf.2022.04.018

M3 - Article

C2 - 35405168

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

Abstract

Keywords

UN SDGs

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