Omicron BA.1-containing mRNA-1273 boosters compared with the original COVID-19 vaccine in the UK: a randomised, observer-blind, active-controlled trial
The omicron BA.1 bivalent booster is used globally. Previous open-label studies of the omicron BA.1 (Moderna mRNA-1273.214) booster showed superior neutralising antibody responses against omicron BA.1 and other variants compared with the original mRNA-1273 booster. We aimed to compare the safety and...
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| Veröffentlicht in: | The Lancet infectious diseases 2023-09, Vol.23 (9), p.1007-1019 |
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| creator | Lee, Ivan T Cosgrove, Catherine A Moore, Patrick Bethune, Claire Nally, Rhiannon Bula, Marcin Kalra, Philip A Clark, Rebecca Dargan, Paul I Boffito, Marta Sheridan, Ray Moran, Ed Darton, Thomas C Burns, Fiona Saralaya, Dinesh Duncan, Christopher J A Lillie, Patrick J San Francisco Ramos, Alberto Galiza, Eva P Heath, Paul T Girard, Bethany Parker, Christy Rust, Dondi Mehta, Shraddha de Windt, Elizabeth Sutherland, Andrea Tomassini, Joanne E Dutko, Frank J Chalkias, Spyros Deng, Weiping Chen, Xing Feng, Jing Tracy, LaRee Zhou, Honghong Miller, Jacqueline M Das, Rituparna Bethune, Claire Boffito, Marta Browne, Duncan Bula, Marcin Burns, Fiona Chadwick, David Clark, Rebecca Cosgrove, Catherine A. Dargan, Paul I. Darton, Thomas C. Duncan, Christopher J.A. Emmett, Stevan Galiza, Eva P. Galloway, James Heath, Paul T. Jones, Lucy Kalra, Philip A. Kaminski, Rachel Lazarus, Rajeka Lillie, Patrick J. Moore, Patrick Moran, Ed Nally, Rhiannon Palfreeman, Adrian Ramos, Alberto San Francisco Rampling, Tommy Sahdev, Anju Saralaya, Dinesh Sheridan, Ray Soiza, Roy |
| description | The omicron BA.1 bivalent booster is used globally. Previous open-label studies of the omicron BA.1 (Moderna mRNA-1273.214) booster showed superior neutralising antibody responses against omicron BA.1 and other variants compared with the original mRNA-1273 booster. We aimed to compare the safety and immunogenicity of omicron BA.1 monovalent and bivalent boosters with the original mRNA-1273 vaccine in a large, randomised controlled trial.
In this large, randomised, observer-blind, active-controlled, phase 3 trial in the UK (28 hospital and vaccination clinic sites), individuals aged 16 years or older who had previously received two injections of any authorised or approved COVID-19 vaccine, with or without an mRNA vaccine booster (third dose), were randomly allocated (1:1) using interactive response technology to receive 50 μg omicron BA.1 monovalent or bivalent vaccines or 50 μg mRNA-1273 administered as boosters via deltoid intramuscular injection. The primary outcomes were safety and immunogenicity at day 29, including prespecified non-inferiority and superiority of booster immune responses, based on the neutralising antibody geometric mean concentration (GMC) ratios of the monovalent and bivalent boosters compared with mRNA-1273. Safety was assessed in all participants who received first or second boosters, and primary immunogenicity outcomes were assessed in all participants who received the planned booster dose, had pre-booster and day 29 antibody data, had no major protocol deviations, and who were SARS-CoV-2-negative. The study is registered with EudraCT (2022-000063-51) and ClinicalTrials.gov (NCT05249829) and is ongoing.
Between Feb 16 and March 24, 2022, 724 participants were randomly allocated to receive omicron BA.1 monovalent (n=366) or mRNA-1273 (n=357), and between April 2 and June 17, 2022, 2824 participants were randomly allocated to receive omicron BA.1 bivalent (n=1418) or mRNA-1273 (n=1395) vaccines as second boosters. Median durations (months) between the most recent COVID-19 vaccine and study boosters were similar for omicron BA.1 monovalent (4·0 months [IQR 3·6–4·7]) and mRNA-1273 (4·1 [3·5–4·7]), and for the omicron BA.1 bivalent (5·5 [4·8–6·2]) and mRNA-1273 (5·4 [4·8–6·2]) boosters. The omicron BA.1 monovalent and bivalent boosters elicited superior neutralising GMCs against the omicron BA.1 variant compared with mRNA-1273, with GMC ratios of 1·68 (99% CI 1·45−1·95) and 1·53 (1·41−1·67) at day 29 post-booster doses in participants |
| doi_str_mv | 10.1016/S1473-3099(23)00295-5 |
| format | Article |
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In this large, randomised, observer-blind, active-controlled, phase 3 trial in the UK (28 hospital and vaccination clinic sites), individuals aged 16 years or older who had previously received two injections of any authorised or approved COVID-19 vaccine, with or without an mRNA vaccine booster (third dose), were randomly allocated (1:1) using interactive response technology to receive 50 μg omicron BA.1 monovalent or bivalent vaccines or 50 μg mRNA-1273 administered as boosters via deltoid intramuscular injection. The primary outcomes were safety and immunogenicity at day 29, including prespecified non-inferiority and superiority of booster immune responses, based on the neutralising antibody geometric mean concentration (GMC) ratios of the monovalent and bivalent boosters compared with mRNA-1273. Safety was assessed in all participants who received first or second boosters, and primary immunogenicity outcomes were assessed in all participants who received the planned booster dose, had pre-booster and day 29 antibody data, had no major protocol deviations, and who were SARS-CoV-2-negative. The study is registered with EudraCT (2022-000063-51) and ClinicalTrials.gov (NCT05249829) and is ongoing.
Between Feb 16 and March 24, 2022, 724 participants were randomly allocated to receive omicron BA.1 monovalent (n=366) or mRNA-1273 (n=357), and between April 2 and June 17, 2022, 2824 participants were randomly allocated to receive omicron BA.1 bivalent (n=1418) or mRNA-1273 (n=1395) vaccines as second boosters. Median durations (months) between the most recent COVID-19 vaccine and study boosters were similar for omicron BA.1 monovalent (4·0 months [IQR 3·6–4·7]) and mRNA-1273 (4·1 [3·5–4·7]), and for the omicron BA.1 bivalent (5·5 [4·8–6·2]) and mRNA-1273 (5·4 [4·8–6·2]) boosters. The omicron BA.1 monovalent and bivalent boosters elicited superior neutralising GMCs against the omicron BA.1 variant compared with mRNA-1273, with GMC ratios of 1·68 (99% CI 1·45−1·95) and 1·53 (1·41−1·67) at day 29 post-booster doses in participants without previous SARS-CoV-2 infection. Both boosters induced non-inferior ancestral SARS-CoV-2 (Asp614Gly) immune responses with GMCs that were similar for the bivalent (2987·2 [95% CI 2814·9–3169·9]) versus mRNA-1273 (2911·3 [2750·9–3081·0]) and lower for the monovalent (2699·7 [2431·3–2997·7] vs 3020·6 [2776·5–3286·2]) boosters, with respective GMC ratios of 1·05 (99% CI 0·96–1·15) and 0·82 (95% CI 0·74–0·91). Results were comparable regardless of previous SARS-CoV-2 infection status. Incidences of solicited adverse reactions with the omicron BA.1 monovalent (335 [91·3%] of 367 participants) and omicron BA.1 bivalent (1285 [90·4%] of 1421 participants) boosters were similar to those observed previously for mRNA-1273, with no new safety concerns identified and no occurrences of fatal adverse events.
Omicron-containing booster vaccines generated superior immunogenicity against omicron BA.1 and comparable immunogenicity against the original strain with no new safety concerns. It remains important to continuously monitor the immune responses and real-world vaccine effectiveness as divergent SARS-CoV-2 variants emerge.
Moderna.</description><identifier>ISSN: 1473-3099</identifier><identifier>EISSN: 1474-4457</identifier><identifier>DOI: 10.1016/S1473-3099(23)00295-5</identifier><identifier>PMID: 37348519</identifier><language>eng</language><publisher>United States: Elsevier Ltd</publisher><subject>2019-nCoV Vaccine mRNA-1273 ; Accountability ; Active control ; Antibodies ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; COVID-19 - prevention & control ; COVID-19 Vaccines ; Humans ; Immune response ; Immunogenicity ; Immunogenicity, Vaccine ; Infectious diseases ; Injections ; mRNA ; Safety ; SARS-CoV-2 - genetics ; Severe acute respiratory syndrome coronavirus 2 ; United Kingdom ; Vaccine efficacy ; Vaccines</subject><ispartof>The Lancet infectious diseases, 2023-09, Vol.23 (9), p.1007-1019</ispartof><rights>2023 Elsevier Ltd</rights><rights>Copyright © 2023 Elsevier Ltd. All rights reserved.</rights><rights>2023. Elsevier Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c440t-bc7ba89f721245e22638795912bde33d35288c458e27b797fd460c5a0dbfade3</citedby><cites>FETCH-LOGICAL-c440t-bc7ba89f721245e22638795912bde33d35288c458e27b797fd460c5a0dbfade3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/2856284646?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976,64364,64366,64368,72218</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37348519$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Ivan T</creatorcontrib><creatorcontrib>Cosgrove, Catherine A</creatorcontrib><creatorcontrib>Moore, Patrick</creatorcontrib><creatorcontrib>Bethune, Claire</creatorcontrib><creatorcontrib>Nally, Rhiannon</creatorcontrib><creatorcontrib>Bula, Marcin</creatorcontrib><creatorcontrib>Kalra, Philip A</creatorcontrib><creatorcontrib>Clark, Rebecca</creatorcontrib><creatorcontrib>Dargan, Paul I</creatorcontrib><creatorcontrib>Boffito, Marta</creatorcontrib><creatorcontrib>Sheridan, Ray</creatorcontrib><creatorcontrib>Moran, Ed</creatorcontrib><creatorcontrib>Darton, Thomas C</creatorcontrib><creatorcontrib>Burns, Fiona</creatorcontrib><creatorcontrib>Saralaya, Dinesh</creatorcontrib><creatorcontrib>Duncan, Christopher J A</creatorcontrib><creatorcontrib>Lillie, Patrick J</creatorcontrib><creatorcontrib>San Francisco Ramos, Alberto</creatorcontrib><creatorcontrib>Galiza, Eva P</creatorcontrib><creatorcontrib>Heath, Paul T</creatorcontrib><creatorcontrib>Girard, Bethany</creatorcontrib><creatorcontrib>Parker, Christy</creatorcontrib><creatorcontrib>Rust, Dondi</creatorcontrib><creatorcontrib>Mehta, Shraddha</creatorcontrib><creatorcontrib>de Windt, Elizabeth</creatorcontrib><creatorcontrib>Sutherland, Andrea</creatorcontrib><creatorcontrib>Tomassini, Joanne E</creatorcontrib><creatorcontrib>Dutko, Frank J</creatorcontrib><creatorcontrib>Chalkias, Spyros</creatorcontrib><creatorcontrib>Deng, Weiping</creatorcontrib><creatorcontrib>Chen, Xing</creatorcontrib><creatorcontrib>Feng, Jing</creatorcontrib><creatorcontrib>Tracy, LaRee</creatorcontrib><creatorcontrib>Zhou, Honghong</creatorcontrib><creatorcontrib>Miller, Jacqueline M</creatorcontrib><creatorcontrib>Das, Rituparna</creatorcontrib><creatorcontrib>Bethune, Claire</creatorcontrib><creatorcontrib>Boffito, Marta</creatorcontrib><creatorcontrib>Browne, Duncan</creatorcontrib><creatorcontrib>Bula, Marcin</creatorcontrib><creatorcontrib>Burns, Fiona</creatorcontrib><creatorcontrib>Chadwick, David</creatorcontrib><creatorcontrib>Clark, Rebecca</creatorcontrib><creatorcontrib>Cosgrove, Catherine A.</creatorcontrib><creatorcontrib>Dargan, Paul I.</creatorcontrib><creatorcontrib>Darton, Thomas C.</creatorcontrib><creatorcontrib>Duncan, Christopher J.A.</creatorcontrib><creatorcontrib>Emmett, Stevan</creatorcontrib><creatorcontrib>Galiza, Eva P.</creatorcontrib><creatorcontrib>Galloway, James</creatorcontrib><creatorcontrib>Heath, Paul T.</creatorcontrib><creatorcontrib>Jones, Lucy</creatorcontrib><creatorcontrib>Kalra, Philip A.</creatorcontrib><creatorcontrib>Kaminski, Rachel</creatorcontrib><creatorcontrib>Lazarus, Rajeka</creatorcontrib><creatorcontrib>Lillie, Patrick J.</creatorcontrib><creatorcontrib>Moore, Patrick</creatorcontrib><creatorcontrib>Moran, Ed</creatorcontrib><creatorcontrib>Nally, Rhiannon</creatorcontrib><creatorcontrib>Palfreeman, Adrian</creatorcontrib><creatorcontrib>Ramos, Alberto San Francisco</creatorcontrib><creatorcontrib>Rampling, Tommy</creatorcontrib><creatorcontrib>Sahdev, Anju</creatorcontrib><creatorcontrib>Saralaya, Dinesh</creatorcontrib><creatorcontrib>Sheridan, Ray</creatorcontrib><creatorcontrib>Soiza, Roy</creatorcontrib><creatorcontrib>Study Investigators</creatorcontrib><title>Omicron BA.1-containing mRNA-1273 boosters compared with the original COVID-19 vaccine in the UK: a randomised, observer-blind, active-controlled trial</title><title>The Lancet infectious diseases</title><addtitle>Lancet Infect Dis</addtitle><description>The omicron BA.1 bivalent booster is used globally. Previous open-label studies of the omicron BA.1 (Moderna mRNA-1273.214) booster showed superior neutralising antibody responses against omicron BA.1 and other variants compared with the original mRNA-1273 booster. We aimed to compare the safety and immunogenicity of omicron BA.1 monovalent and bivalent boosters with the original mRNA-1273 vaccine in a large, randomised controlled trial.
In this large, randomised, observer-blind, active-controlled, phase 3 trial in the UK (28 hospital and vaccination clinic sites), individuals aged 16 years or older who had previously received two injections of any authorised or approved COVID-19 vaccine, with or without an mRNA vaccine booster (third dose), were randomly allocated (1:1) using interactive response technology to receive 50 μg omicron BA.1 monovalent or bivalent vaccines or 50 μg mRNA-1273 administered as boosters via deltoid intramuscular injection. The primary outcomes were safety and immunogenicity at day 29, including prespecified non-inferiority and superiority of booster immune responses, based on the neutralising antibody geometric mean concentration (GMC) ratios of the monovalent and bivalent boosters compared with mRNA-1273. Safety was assessed in all participants who received first or second boosters, and primary immunogenicity outcomes were assessed in all participants who received the planned booster dose, had pre-booster and day 29 antibody data, had no major protocol deviations, and who were SARS-CoV-2-negative. The study is registered with EudraCT (2022-000063-51) and ClinicalTrials.gov (NCT05249829) and is ongoing.
Between Feb 16 and March 24, 2022, 724 participants were randomly allocated to receive omicron BA.1 monovalent (n=366) or mRNA-1273 (n=357), and between April 2 and June 17, 2022, 2824 participants were randomly allocated to receive omicron BA.1 bivalent (n=1418) or mRNA-1273 (n=1395) vaccines as second boosters. Median durations (months) between the most recent COVID-19 vaccine and study boosters were similar for omicron BA.1 monovalent (4·0 months [IQR 3·6–4·7]) and mRNA-1273 (4·1 [3·5–4·7]), and for the omicron BA.1 bivalent (5·5 [4·8–6·2]) and mRNA-1273 (5·4 [4·8–6·2]) boosters. The omicron BA.1 monovalent and bivalent boosters elicited superior neutralising GMCs against the omicron BA.1 variant compared with mRNA-1273, with GMC ratios of 1·68 (99% CI 1·45−1·95) and 1·53 (1·41−1·67) at day 29 post-booster doses in participants without previous SARS-CoV-2 infection. Both boosters induced non-inferior ancestral SARS-CoV-2 (Asp614Gly) immune responses with GMCs that were similar for the bivalent (2987·2 [95% CI 2814·9–3169·9]) versus mRNA-1273 (2911·3 [2750·9–3081·0]) and lower for the monovalent (2699·7 [2431·3–2997·7] vs 3020·6 [2776·5–3286·2]) boosters, with respective GMC ratios of 1·05 (99% CI 0·96–1·15) and 0·82 (95% CI 0·74–0·91). Results were comparable regardless of previous SARS-CoV-2 infection status. Incidences of solicited adverse reactions with the omicron BA.1 monovalent (335 [91·3%] of 367 participants) and omicron BA.1 bivalent (1285 [90·4%] of 1421 participants) boosters were similar to those observed previously for mRNA-1273, with no new safety concerns identified and no occurrences of fatal adverse events.
Omicron-containing booster vaccines generated superior immunogenicity against omicron BA.1 and comparable immunogenicity against the original strain with no new safety concerns. It remains important to continuously monitor the immune responses and real-world vaccine effectiveness as divergent SARS-CoV-2 variants emerge.
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Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>0TZ</scope><scope>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8C2</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope></search><sort><creationdate>202309</creationdate><title>Omicron BA.1-containing mRNA-1273 boosters compared with the original COVID-19 vaccine in the UK: a randomised, observer-blind, active-controlled trial</title><author>Lee, Ivan T ; Cosgrove, Catherine A ; Moore, Patrick ; Bethune, Claire ; Nally, Rhiannon ; Bula, Marcin ; Kalra, Philip A ; Clark, Rebecca ; Dargan, Paul I ; Boffito, Marta ; Sheridan, Ray ; Moran, Ed ; Darton, Thomas C ; Burns, Fiona ; Saralaya, Dinesh ; Duncan, Christopher J A ; Lillie, Patrick J ; San Francisco Ramos, Alberto ; Galiza, Eva P ; Heath, Paul T ; Girard, Bethany ; Parker, Christy ; Rust, Dondi ; Mehta, Shraddha ; de Windt, Elizabeth ; Sutherland, Andrea ; Tomassini, Joanne E ; Dutko, Frank J ; Chalkias, Spyros ; Deng, Weiping ; Chen, Xing ; Feng, Jing ; Tracy, LaRee ; Zhou, Honghong ; Miller, Jacqueline M ; Das, Rituparna ; Bethune, Claire ; Boffito, Marta ; Browne, Duncan ; Bula, Marcin ; Burns, Fiona ; Chadwick, David ; Clark, Rebecca ; Cosgrove, Catherine A. ; Dargan, Paul I. ; Darton, Thomas C. ; Duncan, Christopher J.A. ; Emmett, Stevan ; Galiza, Eva P. ; Galloway, James ; Heath, Paul T. ; Jones, Lucy ; Kalra, Philip A. ; Kaminski, Rachel ; Lazarus, Rajeka ; Lillie, Patrick J. ; Moore, Patrick ; Moran, Ed ; Nally, Rhiannon ; Palfreeman, Adrian ; Ramos, Alberto San Francisco ; Rampling, Tommy ; Sahdev, Anju ; Saralaya, Dinesh ; Sheridan, Ray ; Soiza, Roy</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c440t-bc7ba89f721245e22638795912bde33d35288c458e27b797fd460c5a0dbfade3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>2019-nCoV Vaccine mRNA-1273</topic><topic>Accountability</topic><topic>Active control</topic><topic>Antibodies</topic><topic>Antibodies, Neutralizing</topic><topic>Antibodies, Viral</topic><topic>COVID-19</topic><topic>COVID-19 - prevention & control</topic><topic>COVID-19 Vaccines</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immunogenicity</topic><topic>Immunogenicity, Vaccine</topic><topic>Infectious diseases</topic><topic>Injections</topic><topic>mRNA</topic><topic>Safety</topic><topic>SARS-CoV-2 - genetics</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>United Kingdom</topic><topic>Vaccine efficacy</topic><topic>Vaccines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Ivan T</creatorcontrib><creatorcontrib>Cosgrove, Catherine A</creatorcontrib><creatorcontrib>Moore, Patrick</creatorcontrib><creatorcontrib>Bethune, Claire</creatorcontrib><creatorcontrib>Nally, Rhiannon</creatorcontrib><creatorcontrib>Bula, Marcin</creatorcontrib><creatorcontrib>Kalra, Philip A</creatorcontrib><creatorcontrib>Clark, Rebecca</creatorcontrib><creatorcontrib>Dargan, Paul I</creatorcontrib><creatorcontrib>Boffito, Marta</creatorcontrib><creatorcontrib>Sheridan, Ray</creatorcontrib><creatorcontrib>Moran, Ed</creatorcontrib><creatorcontrib>Darton, Thomas C</creatorcontrib><creatorcontrib>Burns, Fiona</creatorcontrib><creatorcontrib>Saralaya, Dinesh</creatorcontrib><creatorcontrib>Duncan, Christopher J A</creatorcontrib><creatorcontrib>Lillie, Patrick J</creatorcontrib><creatorcontrib>San Francisco Ramos, Alberto</creatorcontrib><creatorcontrib>Galiza, Eva P</creatorcontrib><creatorcontrib>Heath, Paul T</creatorcontrib><creatorcontrib>Girard, Bethany</creatorcontrib><creatorcontrib>Parker, Christy</creatorcontrib><creatorcontrib>Rust, Dondi</creatorcontrib><creatorcontrib>Mehta, Shraddha</creatorcontrib><creatorcontrib>de Windt, Elizabeth</creatorcontrib><creatorcontrib>Sutherland, Andrea</creatorcontrib><creatorcontrib>Tomassini, Joanne E</creatorcontrib><creatorcontrib>Dutko, Frank J</creatorcontrib><creatorcontrib>Chalkias, Spyros</creatorcontrib><creatorcontrib>Deng, Weiping</creatorcontrib><creatorcontrib>Chen, Xing</creatorcontrib><creatorcontrib>Feng, Jing</creatorcontrib><creatorcontrib>Tracy, LaRee</creatorcontrib><creatorcontrib>Zhou, 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Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Ivan T</au><au>Cosgrove, Catherine A</au><au>Moore, Patrick</au><au>Bethune, Claire</au><au>Nally, Rhiannon</au><au>Bula, Marcin</au><au>Kalra, Philip A</au><au>Clark, Rebecca</au><au>Dargan, Paul I</au><au>Boffito, Marta</au><au>Sheridan, Ray</au><au>Moran, Ed</au><au>Darton, Thomas C</au><au>Burns, Fiona</au><au>Saralaya, Dinesh</au><au>Duncan, Christopher J A</au><au>Lillie, Patrick J</au><au>San Francisco Ramos, Alberto</au><au>Galiza, Eva P</au><au>Heath, Paul T</au><au>Girard, Bethany</au><au>Parker, Christy</au><au>Rust, Dondi</au><au>Mehta, Shraddha</au><au>de Windt, Elizabeth</au><au>Sutherland, Andrea</au><au>Tomassini, Joanne E</au><au>Dutko, Frank J</au><au>Chalkias, Spyros</au><au>Deng, Weiping</au><au>Chen, Xing</au><au>Feng, Jing</au><au>Tracy, LaRee</au><au>Zhou, Honghong</au><au>Miller, Jacqueline M</au><au>Das, Rituparna</au><au>Bethune, Claire</au><au>Boffito, Marta</au><au>Browne, Duncan</au><au>Bula, Marcin</au><au>Burns, Fiona</au><au>Chadwick, David</au><au>Clark, Rebecca</au><au>Cosgrove, Catherine A.</au><au>Dargan, Paul I.</au><au>Darton, Thomas C.</au><au>Duncan, Christopher J.A.</au><au>Emmett, Stevan</au><au>Galiza, Eva P.</au><au>Galloway, James</au><au>Heath, Paul T.</au><au>Jones, Lucy</au><au>Kalra, Philip A.</au><au>Kaminski, Rachel</au><au>Lazarus, Rajeka</au><au>Lillie, Patrick J.</au><au>Moore, Patrick</au><au>Moran, Ed</au><au>Nally, Rhiannon</au><au>Palfreeman, Adrian</au><au>Ramos, Alberto San Francisco</au><au>Rampling, Tommy</au><au>Sahdev, Anju</au><au>Saralaya, Dinesh</au><au>Sheridan, Ray</au><au>Soiza, Roy</au><aucorp>Study Investigators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Omicron BA.1-containing mRNA-1273 boosters compared with the original COVID-19 vaccine in the UK: a randomised, observer-blind, active-controlled trial</atitle><jtitle>The Lancet infectious diseases</jtitle><addtitle>Lancet Infect Dis</addtitle><date>2023-09</date><risdate>2023</risdate><volume>23</volume><issue>9</issue><spage>1007</spage><epage>1019</epage><pages>1007-1019</pages><issn>1473-3099</issn><eissn>1474-4457</eissn><abstract>The omicron BA.1 bivalent booster is used globally. Previous open-label studies of the omicron BA.1 (Moderna mRNA-1273.214) booster showed superior neutralising antibody responses against omicron BA.1 and other variants compared with the original mRNA-1273 booster. We aimed to compare the safety and immunogenicity of omicron BA.1 monovalent and bivalent boosters with the original mRNA-1273 vaccine in a large, randomised controlled trial.
In this large, randomised, observer-blind, active-controlled, phase 3 trial in the UK (28 hospital and vaccination clinic sites), individuals aged 16 years or older who had previously received two injections of any authorised or approved COVID-19 vaccine, with or without an mRNA vaccine booster (third dose), were randomly allocated (1:1) using interactive response technology to receive 50 μg omicron BA.1 monovalent or bivalent vaccines or 50 μg mRNA-1273 administered as boosters via deltoid intramuscular injection. The primary outcomes were safety and immunogenicity at day 29, including prespecified non-inferiority and superiority of booster immune responses, based on the neutralising antibody geometric mean concentration (GMC) ratios of the monovalent and bivalent boosters compared with mRNA-1273. Safety was assessed in all participants who received first or second boosters, and primary immunogenicity outcomes were assessed in all participants who received the planned booster dose, had pre-booster and day 29 antibody data, had no major protocol deviations, and who were SARS-CoV-2-negative. The study is registered with EudraCT (2022-000063-51) and ClinicalTrials.gov (NCT05249829) and is ongoing.
Between Feb 16 and March 24, 2022, 724 participants were randomly allocated to receive omicron BA.1 monovalent (n=366) or mRNA-1273 (n=357), and between April 2 and June 17, 2022, 2824 participants were randomly allocated to receive omicron BA.1 bivalent (n=1418) or mRNA-1273 (n=1395) vaccines as second boosters. Median durations (months) between the most recent COVID-19 vaccine and study boosters were similar for omicron BA.1 monovalent (4·0 months [IQR 3·6–4·7]) and mRNA-1273 (4·1 [3·5–4·7]), and for the omicron BA.1 bivalent (5·5 [4·8–6·2]) and mRNA-1273 (5·4 [4·8–6·2]) boosters. The omicron BA.1 monovalent and bivalent boosters elicited superior neutralising GMCs against the omicron BA.1 variant compared with mRNA-1273, with GMC ratios of 1·68 (99% CI 1·45−1·95) and 1·53 (1·41−1·67) at day 29 post-booster doses in participants without previous SARS-CoV-2 infection. Both boosters induced non-inferior ancestral SARS-CoV-2 (Asp614Gly) immune responses with GMCs that were similar for the bivalent (2987·2 [95% CI 2814·9–3169·9]) versus mRNA-1273 (2911·3 [2750·9–3081·0]) and lower for the monovalent (2699·7 [2431·3–2997·7] vs 3020·6 [2776·5–3286·2]) boosters, with respective GMC ratios of 1·05 (99% CI 0·96–1·15) and 0·82 (95% CI 0·74–0·91). Results were comparable regardless of previous SARS-CoV-2 infection status. Incidences of solicited adverse reactions with the omicron BA.1 monovalent (335 [91·3%] of 367 participants) and omicron BA.1 bivalent (1285 [90·4%] of 1421 participants) boosters were similar to those observed previously for mRNA-1273, with no new safety concerns identified and no occurrences of fatal adverse events.
Omicron-containing booster vaccines generated superior immunogenicity against omicron BA.1 and comparable immunogenicity against the original strain with no new safety concerns. It remains important to continuously monitor the immune responses and real-world vaccine effectiveness as divergent SARS-CoV-2 variants emerge.
Moderna.</abstract><cop>United States</cop><pub>Elsevier Ltd</pub><pmid>37348519</pmid><doi>10.1016/S1473-3099(23)00295-5</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1473-3099 |
| ispartof | The Lancet infectious diseases, 2023-09, Vol.23 (9), p.1007-1019 |
| issn | 1473-3099 1474-4457 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2829425525 |
| source | MEDLINE; Elsevier ScienceDirect Journals; ProQuest Central UK/Ireland |
| subjects | 2019-nCoV Vaccine mRNA-1273 Accountability Active control Antibodies Antibodies, Neutralizing Antibodies, Viral COVID-19 COVID-19 - prevention & control COVID-19 Vaccines Humans Immune response Immunogenicity Immunogenicity, Vaccine Infectious diseases Injections mRNA Safety SARS-CoV-2 - genetics Severe acute respiratory syndrome coronavirus 2 United Kingdom Vaccine efficacy Vaccines |
| title | Omicron BA.1-containing mRNA-1273 boosters compared with the original COVID-19 vaccine in the UK: a randomised, observer-blind, active-controlled trial |
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