@article{Munro_A-2021_63521,
title = {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},
author = {Munro, A. and Janani, L. and Cornelius, V. and Aley, P. and Babbage, G. and Baxter, D. and Bula, M. and Cathie, K. and Chatterjee, K. and Dodd, K. and Enever, Y. and Gokani, K. and Goodman, A. and Green, C. and Harndahl, L. and Haughney, J. and Hicks, A. and van der Klaauw, A. and Kwok, J. and Libri, V. and Llewelyn, M. and McGregor, A. and Minassian, A. and Moore, P. and Mughal, M. and Mujadidi, Y. and Murira, J. and Osanlou, O. and Osanlou, R. and Owens, D. and Pacurar, M. and Palfreeman, A. and Pan, D. and Rampling, T. and Regan, K. and Saich, S. and Salkeld, J. and Saralaya, D. and Sharma, S. and Sheridan, R. and Sturdy, A. and Thomson, E. and Todd, S. and Twelves, C. and Read, R. and Charlton, S. and Hallis, B. and Ramsay, M. and Andrews, N. and Nguyen-Van-Tam, J. and Snape, M. and Liu, X. and Faust, S. and Riordan, A. and Ustianowski, A. and Rogers, C. and Hughes, S. and Longshaw, L. and Stockport, J. and Hughes, R. and Grundy, L. and Tudor Jones, L. and Guha, A. and Snashall, E. and Eadsforth, T. and Reeder, S. and Storton, K. and Munusamy, M. and Tandy, B. and Egbo, A. and Cox, S. and Ahmed, N. and Shenoy, A. and Bousfield, R. and Wixted, D. and Gutteridge, H. and Mansfield, B. and Herbert, C. and Holliday, K. and Calderwood, J. and Barker, D. and Brandon, J. and Tulloch, H. and Colquhoun, S. and Thorp, H. and Radford, H. and Evans, J. and Baker, H. and Thorpe, J. and Batham, S. and Hailstone, J. and Phillips, R. and Kumar, D. and Westwell, F. and Makia, F. and Hopkins, N. and Barcella, L. and Mpelembue, M. and Dabagh, M. and Lang, M. and khan, F. and Adebambo, O. and Chita, S. and Corrah, T. and Whittington, A. and John, L. and Roche, S. and Wagstaff, L. and Farrier, A. and Bisnauthsing, K. and Serafimova, T. and Nanino, E. and Cooney, E. and Wilson-Goldsmith, J. and Nguyen, H. and Mazzella, A. and Jackson, B. and Aslam, S. and Bawa, T. and Broadhead, S. and Farooqi, S. and Piper, J. and Weighell, R. and Pickup, L. and Shamtally, D. and Domingo, J. and Kourampa, E. and Hale, C. and Gibney, J. and Stackpoole, M. and Rashid-Gardner, Z. and Lyon, R. and McDonnell, C. and Cole, C. and Stewart, A. and McMillan, G. and Savage, M. and Beckett, H. and Moorbey, C. and Desai, A. and Brown, C. and Naker, K. and Qureshi, E. and Trinham, C. and Sabine, C. and Moore, S. and Hurdover, S. and Justice, E. and Smith, D. and Plested, E. and Ferreira Da Silva, C. and White, R. and Robinson, H. and Cifuentes, L. and Morshead, G. and Drake-Brockman, R. and Kinch, P. and Kasanyinga, M. and Clutterbuck, E. and Bibi, S. and Stuart, A. and Shaw, R. and Singh, M. and Champaneri, T. and Irwin, M. and Khan, M. and Kownacka, A. and Nabunjo, M. and Osuji, C. and Hladkiwskyj, J. and Galvin, D. and Patel, G. and Mouland, J. and Longhurst, B. and Moon, M. and Giddins, B. and Pereira Dias Alves, C. and Richmond, L. and Minnis, C. and Baryschpolec, S. and Elliott, S. and Fox, L. and Graham, V. and Baker, N. and Godwin, K. and Buttigieg, K. and Knight, C. and Brown, P. and Lall, P. and Shaik, I. and Chiplin, E. and Brunt, E. and Leung, S. and Allen, L. and Thomas, S. and Fraser, S. and Choi, B. and Gouriet, J. and Freedman, A. and Perkins, J. and Gowland, A. and MacDonald, J. and Seenan, J. and Starinskij, I. and Seaton, A. and Peters, E. and Singh, S. and Gardside, B. and Bonnaud, A. and Davies, C. and Gordon, E. and Keenan, S. and Hall, J. and Wilkins, S. and Tasker, S. and James, R. and Seath, I. and Littlewood, K. and Newman, J. and Boubriak, I. and Suggitt, D. and Haydock, H. and Bennett, S. and Woodyatt, W. and Hughes, K. and Bell, J. and Coughlan, T. and van Welsenes, D. and Kamal, M. and Cooper, C. and Tunstall, S. and Ronan, N. and Cutts, R. and Dare, T. and Yim, Y. and Whittley, S. and Ricamara, M. and Hamal, S. and Adams, K. and Baker, H. and Driver, K. and Turner, N. and Rawlins, T. and Roy, S. and Merida-Morillas, M. and Sakagami, Y. and Andrews, A. and Goncalves-Cordeiro, L. and Stokes, M. and Ambihapathy, W. and Spencer, J. and Parungao, N. and Berry, L. and Cullinane, J. and Presland, L. and Ross-Russell, A. and Warren, S. and Baker, J. and Oliver, A. and Buadi, A. and Lee, K. and Haskell, L. and Romani, R. and Bentley, I. and Whitbred, T. and Fowler, S. and Gavin, J. and Magee, A. and Watson, T. and Nightingale, K. and Marius, P. and Summerton, E. and Locke, E. and Honey, T. and Lingwood, A. and de la Haye, A. and Elliott, R. and Underwood, K. and King, M. and Davies-Dear, S. and Horsfall, E. and Chalwin, O. and Burton, H. and Edwards, C. and Welham, B. and Garrahy, S. and Hall, F. and Ladikou, E. and Mullan, D. and Hansen, D. and Campbell, M. and Dos Santos, F. and Habash-Bailey, H. and Lakeman, N. and Branney, D. and Vamplew, L. and Hogan, A. and Frankham, J. and Wiselka, M. and Vail, D. and Wenn, V. and Renals, V. and Ellis, K. and Lewis-Taylor, J. and Magan, J. and Hardy, A. and Appleby, K.},
month = {dec},
year = {2021},
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.},
pages = {2258-2276},
volume = {398},
issue = {10318},
journal = {Lancet},
publisher = {Elsevier},
url = {http://dx.doi.org/10.1016/S0140-6736(21)02717-3},
}
