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Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial

Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial
Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial

Background: few data exist on the comparative safety and immunogenicity of different COVID-19 vaccines given as a third (booster) dose. To generate data to optimise selection of booster vaccines, we investigated the reactogenicity and immunogenicity of seven different COVID-19 vaccines as a third dose after two doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd) or BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT).

Methods: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of third dose booster vaccination against COVID-19. Participants were aged older than 30 years, and were at least 70 days post two doses of ChAd or at least 84 days post two doses of BNT primary COVID-19 immunisation course, with no history of laboratory-confirmed SARS-CoV-2 infection. 18 sites were split into three groups (A, B, and C). Within each site group (A, B, or C), participants were randomly assigned to an experimental vaccine or control. Group A received NVX-CoV2373 (Novavax; hereafter referred to as NVX), a half dose of NVX, ChAd, or quadrivalent meningococcal conjugate vaccine (MenACWY)control (1:1:1:1). Group B received BNT, VLA2001 (Valneva; hereafter referred to as VLA), a half dose of VLA, Ad26.COV2.S (Janssen; hereafter referred to as Ad26) or MenACWY (1:1:1:1:1). Group C received mRNA1273 (Moderna; hereafter referred to as m1273), CVnCov (CureVac; hereafter referred to as CVn), a half dose of BNT, or MenACWY (1:1:1:1). Participants and all investigatory staff were blinded to treatment allocation. Coprimary outcomes were safety and reactogenicity and immunogenicity of anti-spike IgG measured by ELISA. The primary analysis for immunogenicity was on a modified intention-to-treat basis; safety and reactogenicity were assessed in the intention-to-treat population. Secondary outcomes included assessment of viral neutralisation and cellular responses. This trial is registered with ISRCTN, number 73765130.

Findings: between June 1 and June 30, 2021, 3498 people were screened. 2878 participants met eligibility criteria and received COVID-19 vaccine or control. The median ages of ChAd/ChAd-primed participants were 53 years (IQR 44-61) in the younger age group and 76 years (73-78) in the older age group. In the BNT/BNT-primed participants, the median ages were 51 years (41-59) in the younger age group and 78 years (75-82) in the older age group. In the ChAd/ChAD-primed group, 676 (46·7%) participants were female and 1380 (95·4%) were White, and in the BNT/BNT-primed group 770 (53·6%) participants were female and 1321 (91·9%) were White. Three vaccines showed overall increased reactogenicity: m1273 after ChAd/ChAd or BNT/BNT; and ChAd and Ad26 after BNT/BNT. For ChAd/ChAd-primed individuals, spike IgG geometric mean ratios (GMRs) between study vaccines and controls ranged from 1·8 (99% CI 1·5-2·3) in the half VLA group to 32·3 (24·8-42·0) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·1 (95% CI 0·7-1·6) for ChAd to 3·6 (2·4-5·5) for m1273. For BNT/BNT-primed individuals, spike IgG GMRs ranged from 1·3 (99% CI 1·0-1·5) in the half VLA group to 11·5 (9·4-14·1) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·0 (95% CI 0·7-1·6) for half VLA to 4·7 (3·1-7·1) for m1273. The results were similar between those aged 30-69 years and those aged 70 years and older. Fatigue and pain were the most common solicited local and systemic adverse events, experienced more in people aged 30-69 years than those aged 70 years or older. Serious adverse events were uncommon, similar in active vaccine and control groups. In total, there were 24 serious adverse events: five in the control group (two in control group A, three in control group B, and zero in control group C), two in Ad26, five in VLA, one in VLA-half, one in BNT, two in BNT-half, two in ChAd, one in CVn, two in NVX, two in NVX-half, and one in m1273.

Interpretation: all study vaccines boosted antibody and neutralising responses after ChAd/ChAd initial course and all except one after BNT/BNT, with no safety concerns. Substantial differences in humoral and cellular responses, and vaccine availability will influence policy choices for booster vaccination.

Funding: UK Vaccine Taskforce and National Institute for Health Research.

Adult, Aged, Aged, 80 and over, BNT162 Vaccine/administration & dosage, COVID-19/immunology, ChAdOx1 nCoV-19/administration & dosage, Female, Humans, Immunization, Secondary/methods, Immunogenicity, Vaccine, Male, Middle Aged, Pandemics, Patient Safety, SARS-CoV-2, United Kingdom
0140-6736
2258-2276
Munro, Alasdair P S
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Pacurar, Mihaela
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Charlton, Sue
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Hallis, Bassam
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Ramsay, Mary
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COV-BOOST study group
Munro, Alasdair P S
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Cathie, Katrina
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Haughney, John
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Hicks, Alexander
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van der Klaauw, Agatha A
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Kwok, Jonathan
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Lambe, Teresa
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Libri, Vincenzo
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Llewelyn, Martin J
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Moore, Patrick
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Murira, Jennifer
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Osanlou, Orod
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Osanlou, Rostam
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Liu, Xinxue
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Faust, Saul N
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Munro, Alasdair P S, Janani, Leila, Cornelius, Victoria, Aley, Parvinder K, Babbage, Gavin, Baxter, David, et al., , Nguyen-Van-Tam, Jonathan, Snape, Matthew D., Liu, Xinxue and Faust, Saul N , COV-BOOST study group (2021) Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial. The Lancet, 398 (10318), 2258-2276. (doi:10.1016/S0140-6736(21)02717-3).

Record type: Article

Abstract

Background: few data exist on the comparative safety and immunogenicity of different COVID-19 vaccines given as a third (booster) dose. To generate data to optimise selection of booster vaccines, we investigated the reactogenicity and immunogenicity of seven different COVID-19 vaccines as a third dose after two doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd) or BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT).

Methods: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of third dose booster vaccination against COVID-19. Participants were aged older than 30 years, and were at least 70 days post two doses of ChAd or at least 84 days post two doses of BNT primary COVID-19 immunisation course, with no history of laboratory-confirmed SARS-CoV-2 infection. 18 sites were split into three groups (A, B, and C). Within each site group (A, B, or C), participants were randomly assigned to an experimental vaccine or control. Group A received NVX-CoV2373 (Novavax; hereafter referred to as NVX), a half dose of NVX, ChAd, or quadrivalent meningococcal conjugate vaccine (MenACWY)control (1:1:1:1). Group B received BNT, VLA2001 (Valneva; hereafter referred to as VLA), a half dose of VLA, Ad26.COV2.S (Janssen; hereafter referred to as Ad26) or MenACWY (1:1:1:1:1). Group C received mRNA1273 (Moderna; hereafter referred to as m1273), CVnCov (CureVac; hereafter referred to as CVn), a half dose of BNT, or MenACWY (1:1:1:1). Participants and all investigatory staff were blinded to treatment allocation. Coprimary outcomes were safety and reactogenicity and immunogenicity of anti-spike IgG measured by ELISA. The primary analysis for immunogenicity was on a modified intention-to-treat basis; safety and reactogenicity were assessed in the intention-to-treat population. Secondary outcomes included assessment of viral neutralisation and cellular responses. This trial is registered with ISRCTN, number 73765130.

Findings: between June 1 and June 30, 2021, 3498 people were screened. 2878 participants met eligibility criteria and received COVID-19 vaccine or control. The median ages of ChAd/ChAd-primed participants were 53 years (IQR 44-61) in the younger age group and 76 years (73-78) in the older age group. In the BNT/BNT-primed participants, the median ages were 51 years (41-59) in the younger age group and 78 years (75-82) in the older age group. In the ChAd/ChAD-primed group, 676 (46·7%) participants were female and 1380 (95·4%) were White, and in the BNT/BNT-primed group 770 (53·6%) participants were female and 1321 (91·9%) were White. Three vaccines showed overall increased reactogenicity: m1273 after ChAd/ChAd or BNT/BNT; and ChAd and Ad26 after BNT/BNT. For ChAd/ChAd-primed individuals, spike IgG geometric mean ratios (GMRs) between study vaccines and controls ranged from 1·8 (99% CI 1·5-2·3) in the half VLA group to 32·3 (24·8-42·0) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·1 (95% CI 0·7-1·6) for ChAd to 3·6 (2·4-5·5) for m1273. For BNT/BNT-primed individuals, spike IgG GMRs ranged from 1·3 (99% CI 1·0-1·5) in the half VLA group to 11·5 (9·4-14·1) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·0 (95% CI 0·7-1·6) for half VLA to 4·7 (3·1-7·1) for m1273. The results were similar between those aged 30-69 years and those aged 70 years and older. Fatigue and pain were the most common solicited local and systemic adverse events, experienced more in people aged 30-69 years than those aged 70 years or older. Serious adverse events were uncommon, similar in active vaccine and control groups. In total, there were 24 serious adverse events: five in the control group (two in control group A, three in control group B, and zero in control group C), two in Ad26, five in VLA, one in VLA-half, one in BNT, two in BNT-half, two in ChAd, one in CVn, two in NVX, two in NVX-half, and one in m1273.

Interpretation: all study vaccines boosted antibody and neutralising responses after ChAd/ChAd initial course and all except one after BNT/BNT, with no safety concerns. Substantial differences in humoral and cellular responses, and vaccine availability will influence policy choices for booster vaccination.

Funding: UK Vaccine Taskforce and National Institute for Health Research.

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e-pub ahead of print date: 2 December 2021
Published date: 18 December 2021
Additional Information: Funding UK Vaccine Taskforce and National Institute for Health Research
Keywords: Adult, Aged, Aged, 80 and over, BNT162 Vaccine/administration & dosage, COVID-19/immunology, ChAdOx1 nCoV-19/administration & dosage, Female, Humans, Immunization, Secondary/methods, Immunogenicity, Vaccine, Male, Middle Aged, Pandemics, Patient Safety, SARS-CoV-2, United Kingdom

Identifiers

Local EPrints ID: 454160
URI: http://eprints.soton.ac.uk/id/eprint/454160
ISSN: 0140-6736
PURE UUID: 4161f5f5-2bb5-4da4-b035-f7444af55011
ORCID for Robert C Read: ORCID iD orcid.org/0000-0002-4297-6728
ORCID for Saul N Faust: ORCID iD orcid.org/0000-0003-3410-7642

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Date deposited: 01 Feb 2022 17:44
Last modified: 16 Aug 2024 01:45

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Contributors

Author: Alasdair P S Munro
Author: Leila Janani
Author: Victoria Cornelius
Author: Parvinder K Aley
Author: Gavin Babbage
Author: David Baxter
Author: et al.
Author: Marcin Bula
Author: Katrina Cathie
Author: Krishna Chatterjee
Author: Kate Dodd
Author: Yvanne Enever
Author: Karishma Gokani
Author: Anna L Goodman
Author: Christopher A Green
Author: Linda Harndahl
Author: John Haughney
Author: Alexander Hicks
Author: Agatha A van der Klaauw
Author: Jonathan Kwok
Author: Teresa Lambe
Author: Vincenzo Libri
Author: Martin J Llewelyn
Author: Alastair C McGregor
Author: Angela M Minassian
Author: Patrick Moore
Author: Mehmood Mughal
Author: Yama F Mujadidi
Author: Jennifer Murira
Author: Orod Osanlou
Author: Rostam Osanlou
Author: Daniel R Owens
Author: Mihaela Pacurar
Author: Adrian Palfreeman
Author: Daniel Pan
Author: Tommy Rampling
Author: Karen Regan
Author: Stephen Saich
Author: Jo Salkeld
Author: Dinesh Saralaya
Author: Sunil Sharma
Author: Ray Sheridan
Author: Ann Sturdy
Author: Emma C Thomson
Author: Shirley Todd
Author: Chris Twelves
Author: Robert C Read ORCID iD
Author: Sue Charlton
Author: Bassam Hallis
Author: Mary Ramsay
Author: Nick J. Andrews
Author: Jonathan Nguyen-Van-Tam
Author: Matthew D. Snape
Author: Xinxue Liu
Author: Saul N Faust ORCID iD
Corporate Author: COV-BOOST study group

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