Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19. The COV-BOOST trial i...

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Published in:The Lancet infectious diseases 2022-08, Vol.22 (8), p.1131-1141
Main Authors: Cathie, Katrina, Chatterjee, Krishna, Harndahl, Linda, Owens, Daniel R, Pacurar, Mihaela, Saich, Stephen, Thomson, Emma C, Todd, Shirley, Read, Robert C, Munro, Alasdair P S, Janani, Leila, Cornelius, Victoria, Aley, Parvinder K, Dodd, Kate, Qureshi, Ehsaan, Llewelyn, Martin J, Mujadidi, Yama F, Osanlou, Rostam, Regan, Karen, Maallah, Mina, Faust, Saul N, Tudor Jones, Lona, Harrison, Elizabeth, Burton, Katharine, Storton, Kim, Munusamy, Malathi, Tandy, Bridget, Cox, Stephen, Barker, Dominique, Hailstone, Jessica, Bisnauthsing, Karen, Abeywickrama, Movin, Spence, Niamh, Packham, Alice, Aslam, Suahil, McGreevy, Caitlin, Borca, Alessandro, Farooqi, Sadaf, Hale, Colin, Stackpoole, Michael, Rashid-Gardner, Zalina, Lyon, Rebecca, McDonnell, Chloe, Cole, Christine, Brown, Claire, Sabine, Charlette, Turnbull, Iain, Drake-Brockman, Rachael, Smith, Catherine, Kownacka, Alicia, Hladkiwskyj, John, Patel, Gita, Barry, Joshua, Longhurst, Beverley, Richmond, Leah, Fox, Lauren, Graham, Victoria, Knight, Chanice, Choi, Bea, Gouriet, Jade, Macdonald, Jonathan, Seaton, Andrew, Gardside, Ben, Bonnaud, Avril, Keenan, Samantha, Hall, Jane, Newman, Joseph, Haydock, Helen, van Welsenes, Donald, Cooper, Chris, Tunstall, Simon, Cutts, Rebecca, Whittley, Sarah, Adams, Kirsty, Turner, Nicola, Andrews, Antonette, Stokes, Matthew, Berry, Lisa, Cullinane, James, Haskell, Louise, Romani, Rossana, Fowler, Simon, Marius, Phedra, Summerton, Eloise, Horsfall, Emily, Burton, Holly, Dineen, Emily, Lakeman, Nicki, Branney, Debbie, Vamplew, Luke, Wiselka, Martin, Wenn, Victoria, Renals, Valerie, Ellis, Kate, Hardy, Anna
Format: Article
Language:English
Subjects:
2019-nCoV Vaccine mRNA-1273
Adverse events
Aged
Antibodies
Antibodies, Viral
BNT162 Vaccine
ChAdOx1 nCoV-19
Clinical trials
Coronaviruses
COVID-19
COVID-19 - prevention & control
COVID-19 vaccines
COVID-19 Vaccines - adverse effects
Dosage
Enzyme-linked immunosorbent assay
Female
Humans
Humoral immunity
Hypothesis testing
Immune response
Immune response (cell-mediated)
Immune system
Immunogenicity
Immunogenicity, Vaccine
Immunoglobulin G
Immunology
Infections
Infectious diseases
Laboratories
Lymphocytes T
Male
Middle Aged
mRNA
mRNA vaccines
Observational studies
Protein folding
Proteins
Randomization
Safety
SARS-CoV-2
Schedules
Severe acute respiratory syndrome coronavirus 2
Spike protein
Statistical analysis
Vaccines
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Summary:Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19. The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 μg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 μg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (anti-spike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing. Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after
ISSN:1473-3099
1474-4457
1474-4457
DOI:10.1016/S1473-3099(22)00271-7