Cargando…

Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials

BACKGROUND: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4–12 weeks. The planned roll-out in the UK will involve vaccinatin...

Descripción completa

Detalles Bibliográficos
Autores principales: Voysey, Merryn, Costa Clemens, Sue Ann, Madhi, Shabir A, Weckx, Lily Y, Folegatti, Pedro M, Aley, Parvinder K, Angus, Brian, Baillie, Vicky L, Barnabas, Shaun L, Bhorat, Qasim E, Bibi, Sagida, Briner, Carmen, Cicconi, Paola, Clutterbuck, Elizabeth A, Collins, Andrea M, Cutland, Clare L, Darton, Thomas C, Dheda, Keertan, Dold, Christina, Duncan, Christopher J A, Emary, Katherine R W, Ewer, Katie J, Flaxman, Amy, Fairlie, Lee, Faust, Saul N, Feng, Shuo, Ferreira, Daniela M, Finn, Adam, Galiza, Eva, Goodman, Anna L, Green, Catherine M, Green, Christopher A, Greenland, Melanie, Hill, Catherine, Hill, Helen C, Hirsch, Ian, Izu, Alane, Jenkin, Daniel, Joe, Carina C D, Kerridge, Simon, Koen, Anthonet, Kwatra, Gaurav, Lazarus, Rajeka, Libri, Vincenzo, Lillie, Patrick J, Marchevsky, Natalie G, Marshall, Richard P, Mendes, Ana V A, Milan, Eveline P, Minassian, Angela M, McGregor, Alastair, Mujadidi, Yama F, Nana, Anusha, Padayachee, Sherman D, Phillips, Daniel J, Pittella, Ana, Plested, Emma, Pollock, Katrina M, Ramasamy, Maheshi N, Ritchie, Adam J, Robinson, Hannah, Schwarzbold, Alexandre V, Smith, Andrew, Song, Rinn, Snape, Matthew D, Sprinz, Eduardo, Sutherland, Rebecca K, Thomson, Emma C, Török, M Estée, Toshner, Mark, Turner, David P J, Vekemans, Johan, Villafana, Tonya L, White, Thomas, Williams, Christopher J, Douglas, Alexander D, Hill, Adrian V S, Lambe, Teresa, Gilbert, Sarah C, Pollard, Andrew J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894131/
https://www.ncbi.nlm.nih.gov/pubmed/33617777
http://dx.doi.org/10.1016/S0140-6736(21)00432-3
_version_ 1783653182905253888
author Voysey, Merryn
Costa Clemens, Sue Ann
Madhi, Shabir A
Weckx, Lily Y
Folegatti, Pedro M
Aley, Parvinder K
Angus, Brian
Baillie, Vicky L
Barnabas, Shaun L
Bhorat, Qasim E
Bibi, Sagida
Briner, Carmen
Cicconi, Paola
Clutterbuck, Elizabeth A
Collins, Andrea M
Cutland, Clare L
Darton, Thomas C
Dheda, Keertan
Dold, Christina
Duncan, Christopher J A
Emary, Katherine R W
Ewer, Katie J
Flaxman, Amy
Fairlie, Lee
Faust, Saul N
Feng, Shuo
Ferreira, Daniela M
Finn, Adam
Galiza, Eva
Goodman, Anna L
Green, Catherine M
Green, Christopher A
Greenland, Melanie
Hill, Catherine
Hill, Helen C
Hirsch, Ian
Izu, Alane
Jenkin, Daniel
Joe, Carina C D
Kerridge, Simon
Koen, Anthonet
Kwatra, Gaurav
Lazarus, Rajeka
Libri, Vincenzo
Lillie, Patrick J
Marchevsky, Natalie G
Marshall, Richard P
Mendes, Ana V A
Milan, Eveline P
Minassian, Angela M
McGregor, Alastair
Mujadidi, Yama F
Nana, Anusha
Padayachee, Sherman D
Phillips, Daniel J
Pittella, Ana
Plested, Emma
Pollock, Katrina M
Ramasamy, Maheshi N
Ritchie, Adam J
Robinson, Hannah
Schwarzbold, Alexandre V
Smith, Andrew
Song, Rinn
Snape, Matthew D
Sprinz, Eduardo
Sutherland, Rebecca K
Thomson, Emma C
Török, M Estée
Toshner, Mark
Turner, David P J
Vekemans, Johan
Villafana, Tonya L
White, Thomas
Williams, Christopher J
Douglas, Alexander D
Hill, Adrian V S
Lambe, Teresa
Gilbert, Sarah C
Pollard, Andrew J
author_facet Voysey, Merryn
Costa Clemens, Sue Ann
Madhi, Shabir A
Weckx, Lily Y
Folegatti, Pedro M
Aley, Parvinder K
Angus, Brian
Baillie, Vicky L
Barnabas, Shaun L
Bhorat, Qasim E
Bibi, Sagida
Briner, Carmen
Cicconi, Paola
Clutterbuck, Elizabeth A
Collins, Andrea M
Cutland, Clare L
Darton, Thomas C
Dheda, Keertan
Dold, Christina
Duncan, Christopher J A
Emary, Katherine R W
Ewer, Katie J
Flaxman, Amy
Fairlie, Lee
Faust, Saul N
Feng, Shuo
Ferreira, Daniela M
Finn, Adam
Galiza, Eva
Goodman, Anna L
Green, Catherine M
Green, Christopher A
Greenland, Melanie
Hill, Catherine
Hill, Helen C
Hirsch, Ian
Izu, Alane
Jenkin, Daniel
Joe, Carina C D
Kerridge, Simon
Koen, Anthonet
Kwatra, Gaurav
Lazarus, Rajeka
Libri, Vincenzo
Lillie, Patrick J
Marchevsky, Natalie G
Marshall, Richard P
Mendes, Ana V A
Milan, Eveline P
Minassian, Angela M
McGregor, Alastair
Mujadidi, Yama F
Nana, Anusha
Padayachee, Sherman D
Phillips, Daniel J
Pittella, Ana
Plested, Emma
Pollock, Katrina M
Ramasamy, Maheshi N
Ritchie, Adam J
Robinson, Hannah
Schwarzbold, Alexandre V
Smith, Andrew
Song, Rinn
Snape, Matthew D
Sprinz, Eduardo
Sutherland, Rebecca K
Thomson, Emma C
Török, M Estée
Toshner, Mark
Turner, David P J
Vekemans, Johan
Villafana, Tonya L
White, Thomas
Williams, Christopher J
Douglas, Alexander D
Hill, Adrian V S
Lambe, Teresa
Gilbert, Sarah C
Pollard, Andrew J
author_sort Voysey, Merryn
collection PubMed
description BACKGROUND: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4–12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. METHODS: We present data from three single-blind randomised controlled trials—one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)—and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 10(10) viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 10(10) viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov, NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). FINDINGS: Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more than 14 days after the second dose. Overall vaccine efficacy more than 14 days after the second dose was 66·7% (95% CI 57·4–74·0), with 84 (1·0%) cases in the 8597 participants in the ChAdOx1 nCoV-19 group and 248 (2·9%) in the 8581 participants in the control group. There were no hospital admissions for COVID-19 in the ChAdOx1 nCoV-19 group after the initial 21-day exclusion period, and 15 in the control group. 108 (0·9%) of 12 282 participants in the ChAdOx1 nCoV-19 group and 127 (1·1%) of 11 962 participants in the control group had serious adverse events. There were seven deaths considered unrelated to vaccination (two in the ChAdOx1 nCov-19 group and five in the control group), including one COVID-19-related death in one participant in the control group. Exploratory analyses showed that vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 after vaccination was 76·0% (59·3–85·9). Our modelling analysis indicated that protection did not wane during this initial 3-month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 (geometric mean ratio [GMR] 0·66 [95% CI 0·59–0·74]). In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81·3% [95% CI 60·3–91·2] at ≥12 weeks) than in those with a short interval (vaccine efficacy 55·1% [33·0–69·9] at <6 weeks). These observations are supported by immunogenicity data that showed binding antibody responses more than two-fold higher after an interval of 12 or more weeks compared with an interval of less than 6 weeks in those who were aged 18–55 years (GMR 2·32 [2·01–2·68]). INTERPRETATION: The results of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with those seen in the interim analysis of the trials and confirm that the vaccine is efficacious, with results varying by dose interval in exploratory analyses. A 3-month dose interval might have advantages over a programme with a short dose interval for roll-out of a pandemic vaccine to protect the largest number of individuals in the population as early as possible when supplies are scarce, while also improving protection after receiving a second dose. FUNDING: UK Research and Innovation, National Institutes of Health Research (NIHR), The Coalition for Epidemic Preparedness Innovations, the Bill & Melinda Gates Foundation, the Lemann Foundation, Rede D’Or, the Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.
format Online
Article
Text
id pubmed-7894131
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-78941312021-02-22 Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials Voysey, Merryn Costa Clemens, Sue Ann Madhi, Shabir A Weckx, Lily Y Folegatti, Pedro M Aley, Parvinder K Angus, Brian Baillie, Vicky L Barnabas, Shaun L Bhorat, Qasim E Bibi, Sagida Briner, Carmen Cicconi, Paola Clutterbuck, Elizabeth A Collins, Andrea M Cutland, Clare L Darton, Thomas C Dheda, Keertan Dold, Christina Duncan, Christopher J A Emary, Katherine R W Ewer, Katie J Flaxman, Amy Fairlie, Lee Faust, Saul N Feng, Shuo Ferreira, Daniela M Finn, Adam Galiza, Eva Goodman, Anna L Green, Catherine M Green, Christopher A Greenland, Melanie Hill, Catherine Hill, Helen C Hirsch, Ian Izu, Alane Jenkin, Daniel Joe, Carina C D Kerridge, Simon Koen, Anthonet Kwatra, Gaurav Lazarus, Rajeka Libri, Vincenzo Lillie, Patrick J Marchevsky, Natalie G Marshall, Richard P Mendes, Ana V A Milan, Eveline P Minassian, Angela M McGregor, Alastair Mujadidi, Yama F Nana, Anusha Padayachee, Sherman D Phillips, Daniel J Pittella, Ana Plested, Emma Pollock, Katrina M Ramasamy, Maheshi N Ritchie, Adam J Robinson, Hannah Schwarzbold, Alexandre V Smith, Andrew Song, Rinn Snape, Matthew D Sprinz, Eduardo Sutherland, Rebecca K Thomson, Emma C Török, M Estée Toshner, Mark Turner, David P J Vekemans, Johan Villafana, Tonya L White, Thomas Williams, Christopher J Douglas, Alexander D Hill, Adrian V S Lambe, Teresa Gilbert, Sarah C Pollard, Andrew J Lancet Articles BACKGROUND: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4–12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. METHODS: We present data from three single-blind randomised controlled trials—one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)—and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 10(10) viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 10(10) viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov, NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). FINDINGS: Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more than 14 days after the second dose. Overall vaccine efficacy more than 14 days after the second dose was 66·7% (95% CI 57·4–74·0), with 84 (1·0%) cases in the 8597 participants in the ChAdOx1 nCoV-19 group and 248 (2·9%) in the 8581 participants in the control group. There were no hospital admissions for COVID-19 in the ChAdOx1 nCoV-19 group after the initial 21-day exclusion period, and 15 in the control group. 108 (0·9%) of 12 282 participants in the ChAdOx1 nCoV-19 group and 127 (1·1%) of 11 962 participants in the control group had serious adverse events. There were seven deaths considered unrelated to vaccination (two in the ChAdOx1 nCov-19 group and five in the control group), including one COVID-19-related death in one participant in the control group. Exploratory analyses showed that vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 after vaccination was 76·0% (59·3–85·9). Our modelling analysis indicated that protection did not wane during this initial 3-month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 (geometric mean ratio [GMR] 0·66 [95% CI 0·59–0·74]). In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81·3% [95% CI 60·3–91·2] at ≥12 weeks) than in those with a short interval (vaccine efficacy 55·1% [33·0–69·9] at <6 weeks). These observations are supported by immunogenicity data that showed binding antibody responses more than two-fold higher after an interval of 12 or more weeks compared with an interval of less than 6 weeks in those who were aged 18–55 years (GMR 2·32 [2·01–2·68]). INTERPRETATION: The results of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with those seen in the interim analysis of the trials and confirm that the vaccine is efficacious, with results varying by dose interval in exploratory analyses. A 3-month dose interval might have advantages over a programme with a short dose interval for roll-out of a pandemic vaccine to protect the largest number of individuals in the population as early as possible when supplies are scarce, while also improving protection after receiving a second dose. FUNDING: UK Research and Innovation, National Institutes of Health Research (NIHR), The Coalition for Epidemic Preparedness Innovations, the Bill & Melinda Gates Foundation, the Lemann Foundation, Rede D’Or, the Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca. Elsevier 2021-03-06 /pmc/articles/PMC7894131/ /pubmed/33617777 http://dx.doi.org/10.1016/S0140-6736(21)00432-3 Text en © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Articles
Voysey, Merryn
Costa Clemens, Sue Ann
Madhi, Shabir A
Weckx, Lily Y
Folegatti, Pedro M
Aley, Parvinder K
Angus, Brian
Baillie, Vicky L
Barnabas, Shaun L
Bhorat, Qasim E
Bibi, Sagida
Briner, Carmen
Cicconi, Paola
Clutterbuck, Elizabeth A
Collins, Andrea M
Cutland, Clare L
Darton, Thomas C
Dheda, Keertan
Dold, Christina
Duncan, Christopher J A
Emary, Katherine R W
Ewer, Katie J
Flaxman, Amy
Fairlie, Lee
Faust, Saul N
Feng, Shuo
Ferreira, Daniela M
Finn, Adam
Galiza, Eva
Goodman, Anna L
Green, Catherine M
Green, Christopher A
Greenland, Melanie
Hill, Catherine
Hill, Helen C
Hirsch, Ian
Izu, Alane
Jenkin, Daniel
Joe, Carina C D
Kerridge, Simon
Koen, Anthonet
Kwatra, Gaurav
Lazarus, Rajeka
Libri, Vincenzo
Lillie, Patrick J
Marchevsky, Natalie G
Marshall, Richard P
Mendes, Ana V A
Milan, Eveline P
Minassian, Angela M
McGregor, Alastair
Mujadidi, Yama F
Nana, Anusha
Padayachee, Sherman D
Phillips, Daniel J
Pittella, Ana
Plested, Emma
Pollock, Katrina M
Ramasamy, Maheshi N
Ritchie, Adam J
Robinson, Hannah
Schwarzbold, Alexandre V
Smith, Andrew
Song, Rinn
Snape, Matthew D
Sprinz, Eduardo
Sutherland, Rebecca K
Thomson, Emma C
Török, M Estée
Toshner, Mark
Turner, David P J
Vekemans, Johan
Villafana, Tonya L
White, Thomas
Williams, Christopher J
Douglas, Alexander D
Hill, Adrian V S
Lambe, Teresa
Gilbert, Sarah C
Pollard, Andrew J
Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials
title Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials
title_full Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials
title_fullStr Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials
title_full_unstemmed Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials
title_short Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials
title_sort single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of chadox1 ncov-19 (azd1222) vaccine: a pooled analysis of four randomised trials
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894131/
https://www.ncbi.nlm.nih.gov/pubmed/33617777
http://dx.doi.org/10.1016/S0140-6736(21)00432-3
work_keys_str_mv AT voyseymerryn singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT costaclemenssueann singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT madhishabira singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT weckxlilyy singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT folegattipedrom singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT aleyparvinderk singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT angusbrian singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT baillievickyl singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT barnabasshaunl singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT bhoratqasime singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT bibisagida singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT brinercarmen singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT cicconipaola singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT clutterbuckelizabetha singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT collinsandream singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT cutlandclarel singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT dartonthomasc singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT dhedakeertan singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT doldchristina singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT duncanchristopherja singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT emarykatherinerw singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT ewerkatiej singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT flaxmanamy singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT fairlielee singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT faustsauln singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT fengshuo singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT ferreiradanielam singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT finnadam singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT galizaeva singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT goodmanannal singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT greencatherinem singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT greenchristophera singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT greenlandmelanie singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT hillcatherine singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT hillhelenc singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT hirschian singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT izualane singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT jenkindaniel singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT joecarinacd singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT kerridgesimon singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT koenanthonet singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT kwatragaurav singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT lazarusrajeka singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT librivincenzo singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT lilliepatrickj singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT marchevskynatalieg singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT marshallrichardp singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT mendesanava singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT milanevelinep singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT minassianangelam singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT mcgregoralastair singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT mujadidiyamaf singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT nanaanusha singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT padayacheeshermand singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT phillipsdanielj singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT pittellaana singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT plestedemma singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT pollockkatrinam singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT ramasamymaheshin singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT ritchieadamj singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT robinsonhannah singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT schwarzboldalexandrev singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT smithandrew singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT songrinn singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT snapematthewd singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT sprinzeduardo singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT sutherlandrebeccak singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT thomsonemmac singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT torokmestee singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT toshnermark singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT turnerdavidpj singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT vekemansjohan singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT villafanatonyal singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT whitethomas singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT williamschristopherj singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT douglasalexanderd singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT hilladrianvs singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT lambeteresa singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT gilbertsarahc singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT pollardandrewj singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials
AT singledoseadministrationandtheinfluenceofthetimingoftheboosterdoseonimmunogenicityandefficacyofchadox1ncov19azd1222vaccineapooledanalysisoffourrandomisedtrials