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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

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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. / Munro, Alasdair P S; Feng, Shuo; Janani, Leila et al.
In: Lancet Infectious Diseases, Vol. 22, No. 8, 01.08.2022, p. 1131-1141.

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

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Munro, APS, Feng, S, Janani, L, Cornelius, V, Aley, PK, Babbage, G, Baxter, D, Bula, M, Cathie, K, Chatterjee, K, Dodd, K, Enever, Y, Qureshi, E, Goodman, AL, Green, CA, Harndahl, L, Haughney, J, Hicks, A, Klaauw, AAVD, Kanji, N, Libri, V, Llewelyn, MJ, McGregor, AC, Maallah, M, 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, Bawa, T, Saralaya, D, Sharma, S, Sheridan, R, Thomson, EC, Todd, S, Twelves, C, Read, RC, Charlton, S, Hallis, B, Ramsay, M, Andrews, N, Lambe, T, Nguyen-Van-Tam, JS, Snape, MD, Liu, X, Faust, SN, Munro, APS, Feng, S, Janani, L, Cornelius, V, Aley, PK, Babbage, G, Baxter, D, Bula, M, Cathie, K, Chatterjee, K, Dodd, K, Enever, Y, Qureshi, E, Goodman, AL, Green, CA, Harndahl, L, Haughney, J, Hicks, A, Klaauw, AAVD, Kanji, N, 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, Bawa, T, Saralaya, D, Sharma, S, Sheridan, R, Maallah, M, Thomson, EC, Todd, S, Twelves, C, Read, RC, Charlton, S, Hallis, B, Ramsay, M, Andrews, N, Lambe, T, Nguyen-Van-Tam, JS, Snape, MD, Liu, X, Faust, SN, Riordan, A, Ustianowski, A, Rogers, C, Katechia, K, Cooper, A, Freedman, A, Hughes, R, Grundy, L, Jones, LT, Harrison, E, Snashall, E, Mallon, L, Burton, K, Storton, K, Munusamy, M, Tandy, B, Egbo, A, Cox, S, Ahmed, NN, Shenoy, A, Bousfield, R, Wixted, D, Gutteridge, H, Mansfield, B, Herbert, C, Murira, J, Calderwood, J, Barker, D, Brandon, J, Tulloch, H, Colquhoun, S, Thorp, H, Radford, H, Evans, J, Baker, H, Thorpe, J, Batham, S, Hailstone, J, Phillips, R, Kumar, D, Westwell, F, Sturdy, A, Barcella, L, Soussi, N, Mpelembue, M, Raj, S, Sharma, R, Corrah, T, John, L, Whittington, A, Roche, S, Wagstaff, L, Farrier, A, Bisnauthsing, K, Abeywickrama, M, Spence, N, Packham, A, Serafimova, T, Aslam, S, McGreevy, C, Borca, A, DeLosSantosDominguez, P, Palmer, E, Broadhead, S, Farooqi, S, Piper, J, Weighell, R, Pickup, L, Shamtally, D, Domingo, J, Kourampa, E, Hale, C, Gibney, J, Stackpoole, M, Rashid-Gardner, Z, Lyon, R, McDonnell, C, Cole, C, Stewart, A, McMillan, G, Savage, M, Beckett, H, Moorbey, C, Desai, A, Brown, C, Naker, K, Gokani, K, Trinham, C, Sabine, C, Moore, S, Hurdover, S, Justice, E, Stone, M, Plested, E, Silva, CFD, White, R, Robinson, H, Turnbull, I, Morshead, G, Drake-Brockman, R, Smith, C, Li, G, Kasanyinga, M, Clutterbuck, EA, Bibi, S, Singh, M, Champaneri, T, Irwin, M, Khan, M, Kownacka, A, Nabunjo, M, Osuji, C, Hladkiwskyj, J, Galvin, D, Patel, G, Grierson, J, Males, S, Askoolam, K, Barry, J, Mouland, J, Longhurst, B, Moon, M, Giddins, B, Alves, CPD, Richmond, L, Minnis, C, Baryschpolec, S, Elliott, S, Fox, L, Graham, V, Baker, N, Godwin, K, Buttigieg, K, Knight, C, Brown, P, Lall, P, Shaik, I, Chiplin, E, Brunt, E, Leung, S, Allen, L, Thomas, S, Fraser, S, Choi, B, Gouriet, J, Perkins, J, Gowland, A, Macdonald, J, Seenan, JP, Starinskij, I, Seaton, A, Peters, E, Singh, S, Gardside, B, Bonnaud, A, Davies, C, Gordon, E, Keenan, S, Hall, J, Wilkins, S, Tasker, S, James, R, Seath, I, Littlewood, K, Newman, J, Boubriak, I, Suggitt, D, Haydock, H, Bennett, S, Woodyatt, W, Hughes, K, Bell, J, Coughlan, T, Welsenes, DV, Kamal, M, Cooper, C, Tunstall, S, Ronan, N, Cutts, R, Dare, T, Yim, YTN, Whittley, S, Hamal, S, Ricamara, M, Adams, K, Baker, H, Driver, K, Turner, N, Rawlins, T, Roy, S, Merida-Morillas, M, Sakagami, Y, Andrews, A, Goncalvescordeiro, L, Stokes, M, Ambihapathy, W, Spencer, J, Parungao, N, Berry, L, Cullinane, J, Presland, L, Russell, AR, Warren, S, Baker, J, Oliver, A, Buadi, A, Lee, K, Haskell, L, Romani, R, Bentley, I, Whitbred, T, Fowler, S, Gavin, J, Magee, A, Watson, T, Nightingale, K, Marius, P, Summerton, E, Locke, E, Honey, T, Lingwood, A, Haye, ADL, Elliott, RS, Underwood, K, King, M, Davies-Dear, S, Horsfall, E, Chalwin, O, Burton, H, Edwards, CJ, Welham, B, Appleby, K, Dineen, E, Garrahy, S, Hall, F, Ladikou, E, Mullan, D, Hansen, D, Campbell, M, Santos, FD, Lakeman, N, Branney, D, Vamplew, L, Hogan, A, Frankham, J, Wiselka, M, Vail, D, Wenn, V, Renals, V, Ellis, K, Lewis-Taylor, J, Habash-Bailey, H, Magan, J & Hardy, A 2022, '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', Lancet Infectious Diseases, vol. 22, no. 8, pp. 1131-1141. https://doi.org/10.1016/S1473-3099(22)00271-7

APA

Munro, A. P. S., Feng, S., Janani, L., Cornelius, V., Aley, P. K., Babbage, G., Baxter, D., Bula, M., Cathie, K., Chatterjee, K., Dodd, K., Enever, Y., Qureshi, E., Goodman, A. L., Green, C. A., Harndahl, L., Haughney, J., Hicks, A., Klaauw, A. A. V. D., ... Hardy, A. (2022). 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. Lancet Infectious Diseases, 22(8), 1131-1141. https://doi.org/10.1016/S1473-3099(22)00271-7

CBE

Munro APS, Feng S, Janani L, Cornelius V, Aley PK, Babbage G, Baxter D, Bula M, Cathie K, Chatterjee K, et al. 2022. 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. Lancet Infectious Diseases. 22(8):1131-1141. https://doi.org/10.1016/S1473-3099(22)00271-7

MLA

Munro, Alasdair P S et al. "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". Lancet Infectious Diseases. 2022, 22(8). 1131-1141. https://doi.org/10.1016/S1473-3099(22)00271-7

VancouverVancouver

Munro APS, Feng S, Janani L, Cornelius V, Aley PK, Babbage G et al. 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. Lancet Infectious Diseases. 2022 Aug 1;22(8):1131-1141. Epub 2022 May 9. doi: 10.1016/S1473-3099(22)00271-7

Author

Munro, Alasdair P S ; Feng, Shuo ; Janani, Leila et al. / 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. In: Lancet Infectious Diseases. 2022 ; Vol. 22, No. 8. pp. 1131-1141.

RIS

TY - JOUR

T1 - 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

AU - Munro, Alasdair P S

AU - Feng, Shuo

AU - Janani, Leila

AU - Cornelius, Victoria

AU - Aley, Parvinder K

AU - Babbage, Gavin

AU - Baxter, David

AU - Bula, Marcin

AU - Cathie, Katrina

AU - Chatterjee, Krishna

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 - Klaauw, Agatha A van der

AU - Kanji, Nasir

AU - Libri, Vincenzo

AU - Llewelyn, Martin J

AU - McGregor, Alastair C

AU - Maallah, Mina

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 - Bawa, Tanveer

AU - Saralaya, Dinesh

AU - Sharma, Sunil

AU - Sheridan, Ray

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 - Snape, Matthew D

AU - Liu, Xinxue

AU - Faust, Saul N

AU - Munro, Alasdair P S

AU - Feng, Shuo

AU - Janani, Leila

AU - Cornelius, Victoria

AU - Aley, Parvinder K

AU - Babbage, Gavin

AU - Baxter, David

AU - Bula, Marcin

AU - Cathie, Katrina

AU - Chatterjee, Krishna

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 - Klaauw, Agatha A van der

AU - Kanji, Nasir

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 - Bawa, Tanveer

AU - Saralaya, Dinesh

AU - Sharma, Sunil

AU - Sheridan, Ray

AU - Maallah, Mina

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 - Snape, Matthew D

AU - Liu, Xinxue

AU - Faust, Saul N

AU - Riordan, Andrew

AU - Ustianowski, Andrew

AU - Rogers, Chris

AU - Katechia, Kashyap

AU - Cooper, Alison

AU - Freedman, Andrew

AU - Hughes, Rachel

AU - Grundy, Lynne

AU - Jones, Lona Tudor

AU - Harrison, Elizabeth

AU - Snashall, Emma

AU - Mallon, Lewis

AU - Burton, Katharine

AU - Storton, Kim

AU - Munusamy, Malathi

AU - Tandy, Bridget

AU - Egbo, Akamino

AU - Cox, Stephen

AU - Ahmed, Nabeela Nazir

AU - Shenoy, Anil

AU - Bousfield, Rachel

AU - Wixted, Donna

AU - Gutteridge, Helen

AU - Mansfield, Becky

AU - Herbert, Christopher

AU - Murira, Jennifer

AU - Calderwood, James

AU - Barker, Dominique

AU - Brandon, Jacqueline

AU - Tulloch, Hayley

AU - Colquhoun, Suzie

AU - Thorp, Helen

AU - Radford, Helen

AU - Evans, Julie

AU - Baker, Helena

AU - Thorpe, Jeanette

AU - Batham, Sally

AU - Hailstone, Jessica

AU - Phillips, Rachael

AU - Kumar, Dileep

AU - Westwell, Fran

AU - Sturdy, Ann

AU - Barcella, Lara

AU - Soussi, Najwa

AU - Mpelembue, Mushiya

AU - Raj, Sreena

AU - Sharma, Rajni

AU - Corrah, Tumena

AU - John, Laurence

AU - Whittington, Ashley

AU - Roche, Siobhan

AU - Wagstaff, Lynda

AU - Farrier, Adam

AU - Bisnauthsing, Karen

AU - Abeywickrama, Movin

AU - Spence, Niamh

AU - Packham, Alice

AU - Serafimova, Teona

AU - Aslam, Suahil

AU - McGreevy, Caitlin

AU - Borca, Alessandro

AU - DeLosSantosDominguez, Pamela

AU - Palmer, Emily

AU - Broadhead, Samantha

AU - Farooqi, Sadaf

AU - Piper, Jo

AU - Weighell, Rowena

AU - Pickup, Lorinda

AU - Shamtally, Djamila

AU - Domingo, Jason

AU - Kourampa, Evgenia

AU - Hale, Colin

AU - Gibney, Jennifer

AU - Stackpoole, Michael

AU - Rashid-Gardner, Zalina

AU - Lyon, Rebecca

AU - McDonnell, Chloe

AU - Cole, Christine

AU - Stewart, Anna

AU - McMillan, Gillian

AU - Savage, Mary

AU - Beckett, Helen

AU - Moorbey, Chantelle

AU - Desai, Amisha

AU - Brown, Claire

AU - Naker, Kush

AU - Gokani, Karishma

AU - Trinham, Charlotte

AU - Sabine, Charlette

AU - Moore, Sophie

AU - Hurdover, Steve

AU - Justice, Edwin

AU - Stone, Megan

AU - Plested, Emma

AU - Silva, Carla Ferreira Da

AU - White, Rachel

AU - Robinson, Hannah

AU - Turnbull, Iain

AU - Morshead, Gertraud

AU - Drake-Brockman, Rachael

AU - Smith, Catherine

AU - Li, Grace

AU - Kasanyinga, Mwila

AU - Clutterbuck, Elizabeth A

AU - Bibi, Sagida

AU - Singh, Michael

AU - Champaneri, Trishna

AU - Irwin, Margaret

AU - Khan, Mohammed

AU - Kownacka, Alicia

AU - Nabunjo, Martha

AU - Osuji, Carol

AU - Hladkiwskyj, John

AU - Galvin, Dominic

AU - Patel, Gita

AU - Grierson, Jacques

AU - Males, Samantha

AU - Askoolam, Krishna

AU - Barry, Joshua

AU - Mouland, Johanna

AU - Longhurst, Beverley

AU - Moon, Maria

AU - Giddins, Beth

AU - Alves, Carlota Pereira Dias

AU - Richmond, Leah

AU - Minnis, Christine

AU - Baryschpolec, Sonia

AU - Elliott, Scott

AU - Fox, Lauren

AU - Graham, Victoria

AU - Baker, Natalie

AU - Godwin, Kerry

AU - Buttigieg, Karen

AU - Knight, Chanice

AU - Brown, Phillip

AU - Lall, Paminder

AU - Shaik, Imam

AU - Chiplin, Emily

AU - Brunt, Emily

AU - Leung, Stephanie

AU - Allen, Lauren

AU - Thomas, Steve

AU - Fraser, Sara

AU - Choi, Bea

AU - Gouriet, Jade

AU - Perkins, Jonathan

AU - Gowland, Andrew

AU - Macdonald, Jonathan

AU - Seenan, John Paul

AU - Starinskij, Igor

AU - Seaton, Andrew

AU - Peters, Erica

AU - Singh, Stephen

AU - Gardside, Ben

AU - Bonnaud, Avril

AU - Davies, Ceri

AU - Gordon, Elizabeth

AU - Keenan, Samantha

AU - Hall, Jane

AU - Wilkins, Suzanne

AU - Tasker, Suzanne

AU - James, Rob

AU - Seath, Ingrid

AU - Littlewood, Kelly

AU - Newman, Joseph

AU - Boubriak, Iryna

AU - Suggitt, Debbie

AU - Haydock, Helen

AU - Bennett, Sara

AU - Woodyatt, Wiesia

AU - Hughes, Kerry

AU - Bell, Judith

AU - Coughlan, Tricia

AU - Welsenes, Donald van

AU - Kamal, Mohammed

AU - Cooper, Chris

AU - Tunstall, Simon

AU - Ronan, Nicholas

AU - Cutts, Rebecca

AU - Dare, Tracey

AU - Yim, Yee Ting Nicole

AU - Whittley, Sarah

AU - Hamal, Shama

AU - Ricamara, Marivic

AU - Adams, Kirsty

AU - Baker, Holly

AU - Driver, Kimberley

AU - Turner, Nicola

AU - Rawlins, Todd

AU - Roy, Subarna

AU - Merida-Morillas, Marta

AU - Sakagami, Yukari

AU - Andrews, Antonette

AU - Goncalvescordeiro, Lillian

AU - Stokes, Matthew

AU - Ambihapathy, Wythehi

AU - Spencer, Joanne

AU - Parungao, Nina

AU - Berry, Lisa

AU - Cullinane, James

AU - Presland, Laura

AU - Russell, Amy Ross

AU - Warren, Sarah

AU - Baker, Jonathan

AU - Oliver, Abigail

AU - Buadi, Amanda

AU - Lee, Kim

AU - Haskell, Louise

AU - Romani, Rossana

AU - Bentley, Ian

AU - Whitbred, Tim

AU - Fowler, Simon

AU - Gavin, John

AU - Magee, Alan

AU - Watson, Tara

AU - Nightingale, Kari

AU - Marius, Phedra

AU - Summerton, Eloise

AU - Locke, Emily

AU - Honey, Thomas

AU - Lingwood, Aidan

AU - Haye, Anastasia de la

AU - Elliott, Ryan Stephen

AU - Underwood, Karen

AU - King, Mikayala

AU - Davies-Dear, Sharon

AU - Horsfall, Emily

AU - Chalwin, Olivia

AU - Burton, Holly

AU - Edwards, Christopher J

AU - Welham, Benjamin

AU - Appleby, Kim

AU - Dineen, Emily

AU - Garrahy, Sarah

AU - Hall, Fran

AU - Ladikou, Eleni

AU - Mullan, Dee

AU - Hansen, Daniel

AU - Campbell, Marion

AU - Santos, Filipa Dos

AU - Lakeman, Nicki

AU - Branney, Debbie

AU - Vamplew, Luke

AU - Hogan, Alison

AU - Frankham, Jorden

AU - Wiselka, Martin

AU - Vail, Denny

AU - Wenn, Victoria

AU - Renals, Valerie

AU - Ellis, Kate

AU - Lewis-Taylor, Jessica

AU - Habash-Bailey, Haniah

AU - Magan, Javier

AU - Hardy, Anna

PY - 2022/8/1

Y1 - 2022/8/1

N2 - Summary Background 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. Methods 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. Findings 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 the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group). Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose. Funding UK Vaccine Task Force and National Institute for Health Research.

AB - Summary Background 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. Methods 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. Findings 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 the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group). Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose. Funding UK Vaccine Task Force and National Institute for Health Research.

U2 - 10.1016/S1473-3099(22)00271-7

DO - 10.1016/S1473-3099(22)00271-7

M3 - Article

VL - 22

SP - 1131

EP - 1141

JO - Lancet Infectious Diseases

JF - Lancet Infectious Diseases

SN - 1473-3099

IS - 8

ER -