المؤلفون: Shaw, RH, Greenland, M, Stuart, AS, Aley, PK, Andrews, NJ, Cameron, JC, Charlton, S, Clutterbuck, EA, Collins, AM, Darton, T, Dinesh, T, Duncan, CJ, Faust, SN, Ferreira, DM, Finn, A, Goodman, AL, Green, CA, Hallis, B, Heath, PT, Hill, H, Lambe, T, Libri, V, Lillie, PJ, Morey, E, Mujadidi, YF, Payne, R, Plested, EL, Provstgaard-Morys, S, Ramasamy, MN, Mary Ramsay, F, Read, RC, Hannah Robinson, RN, Screaton, GR, Singh, N, Turner, DP, Turner, PJ, Rachel White, RN, Nguyen-Van-Tam, JS, Liu, X, Snape, MD

المساهمون: Group, Com-COV2 Study

الوصف: Background Heterologous COVID vaccine priming schedules are immunogenic and effective. This report aims to understand the persistence of immune response to the viral vectored, mRNA and protein-based COVID-19 vaccine platforms used in homologous and heterologous priming combinations, which will inform the choice of vaccine platform in future vaccine development. Methods Com-COV2 was a single-blinded trial in which adults ≥ 50 years, previously immunised with single dose ‘ChAd’ (ChAdOx1 nCoV-19, AZD1222, Vaxzevria, Astrazeneca) or ‘BNT’ (BNT162b2, tozinameran, Comirnaty, Pfizer/BioNTech), were randomised 1:1:1 to receive a second dose 8–12 weeks later with either the homologous vaccine, or ‘Mod’ (mRNA-1273, Spikevax, Moderna) or ‘NVX’ (NVX-CoV2373, Nuvaxovid, Novavax). Immunological follow-up and the secondary objective of safety monitoring were performed over nine months. Analyses of antibody and cellular assays were performed on an intention-to-treat population without evidence of COVID-19 infection at baseline or for the trial duration. Findings In April/May 2021, 1072 participants were enrolled at a median of 9.4 weeks after receipt of a single dose of ChAd (N = 540, 45% female) or BNT (N = 532, 39% female) as part of the national vaccination programme. In ChAd-primed participants, ChAd/Mod had the highest anti-spike IgG from day 28 through to 6 months, although the heterologous vs homologous geometric mean ratio (GMR) dropped from 9.7 (95% CI (confidence interval): 8.2, 11.5) at D28 to 6.2 (95% CI: 5.0, 7.7) at D196. The heterologous/homologous GMR for ChAd/NVX similarly dropped from 3.0 (95% CI:2.5,3.5) to 2.4 (95% CI:1.9, 3.0). In BNT-primed participants, decay was similar between heterologous and homologous schedules with BNT/Mod inducing the highest anti-spike IgG for the duration of follow-up. The adjusted GMR (aGMR) for BNT/Mod compared with BNT/BNT increased from 1.36 (95% CI: 1.17, 1.58) at D28 to 1.52 (95% CI: 1.21, 1.90) at D196, whilst for BNT/NVX this aGMR was 0.55 (95% CI: 0.47, 0.64) at day 28 ...

العلاقة: https://ora.ox.ac.uk/objects/uuid:bcc82eea-20e2-4846-a8a1-68083bb0e886Test; https://doi.org/10.1016/j.jinf.2023.03.027Test

الإتاحة: https://doi.org/10.1016/j.jinf.2023.03.027Test
https://ora.ox.ac.uk/objects/uuid:bcc82eea-20e2-4846-a8a1-68083bb0e886Test

المؤلفون: Liu, X, Munro, APS, Wright, A, Feng, S, Janani, L, Aley, PK, Babbage, G, Baker, J, Baxter, D, Bawa, T, Bula, M, Cathie, K, Chatterjee, K, Dodd, K, Enever, Y, Fox, L, Qureshi, E, Goodman, AL, Green, CA, Haughney, J, Hicks, A, Jones, CE, Kanji, N, van der Klaauw, AA, Libri, V, Llewelyn, MJ, Mansfield, R, Maallah, M, McGregor, AC, Minassian, AM, Moore, P, Mughal, M, Mujadidi, YF, Belhadef, HT, Holliday, K, Osanlou, O, Osanlou, R, Owens, DR, Pacurar, M, Palfreeman, A, Pan, D, Rampling, T, Regan, K, Saich, S, Saralaya, D, Sharma, S, Sheridan, R, Stokes, M, Thomson, EC, Todd, S, Twelves, C, Read, RC, Charlton, S, Hallis, B, Ramsay, M, Andrews, N, Lambe, T, Nguyen-Van-Tam, JS, Cornelius, V, Snape, MD, Faust, SN

المصدر: Journal of Infection , 87 (1) pp. 18-26. (2023)

مصطلحات موضوعية: Antibodies, Boosters, COVID-19, Immunisation, Immunogenicity, SARS-CoV-2, T-Cells, Vaccination

الوصف: Background: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose in June 2021. Monovalent messenger RNA (mRNA) COVID-19 vaccines were subsequently widely used for the third and fourth-dose vaccination campaigns in high-income countries. Real-world vaccine effectiveness against symptomatic infections following third doses declined during the Omicron wave. This report compares the immunogenicity and kinetics of responses to third doses of vaccines from day (D) 28 to D242 following third doses in seven study arms. Methods: The trial initially included ten experimental vaccine arms (seven full-dose, three half-dose) delivered at three groups of six sites. Participants in each site group were randomised to three or four experimental vaccines, or MenACWY control. The trial was stratified such that half of participants had previously received two primary doses of ChAdOx1 nCov-19 (Oxford–AstraZeneca; hereafter referred to as ChAd) and half had received two doses of BNT162b2 (Pfizer–BioNtech, hereafter referred to as BNT). The D242 follow-up was done in seven arms (five full-dose, two half-dose). The BNT vaccine was used as the reference as it was the most commonly deployed third-dose vaccine in clinical practice in high-income countries. The primary analysis was conducted using all randomised and baseline seronegative participants who were SARS-CoV-2 naïve during the study and who had not received a further COVID-19 vaccine for any reason since third dose randomisation. Results: Among the 817 participants included in this report, the median age was 72 years (IQR: 55–78) with 50.7% being female. The decay rates of anti-spike IgG between vaccines are different among both populations who received initial doses of ChAd/ChAd and BNT/BNT. In the population that previously received ChAd/ChAd, mRNA vaccines had the highest titre at D242 following their vaccine dose although Ad26. COV2. S (Janssen; hereafter referred to as Ad26) showed slower decay. For people ...

وصف الملف: application/pdf

العلاقة: https://discovery.ucl.ac.uk/id/eprint/10171907/1/1-s2.0-S0163445323002475-main.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10171907Test/

الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10171907/1/1-s2.0-S0163445323002475-main.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10171907Test/

المؤلفون: Little, P, Francis, NA, Stuart, B, O'Reilly, G, Thompson, N, Becque, T, Hay, AD, Wang, K, Sharland, M, Harnden, A, Yao, G, Raftery, J, Zhu, S, Little, J, Hookham, C, Rowley, K, Euden, J, Harman, K, Coenen, S, Read, RC, Woods, C, Butler, CC, Faust, SN, Leydon, G, Wan, M, Hood, K, Whitehurst, J, Richards-Hall, S, Smith, P, Thomas, M, Moore, M, Verheij, T

الوصف: BACKGROUND: Antimicrobial resistance is a global health threat. Antibiotics are commonly prescribed for children with uncomplicated lower respiratory tract infections, but there is little randomised evidence to support the effectiveness of antibiotics in treating these infections, either overall or relating to key clinical subgroups in which antibiotic prescribing is common (chest signs; fever; physician rating of unwell; sputum/rattly chest; shortness of breath). OBJECTIVES: To estimate the clinical effectiveness and cost-effectiveness of amoxicillin for uncomplicated lower respiratory tract infections in children both overall and in clinical subgroups. DESIGN: Placebo-controlled trial with qualitative, observational and cost-effectiveness studies. SETTING: UK general practices. PARTICIPANTS: Children aged 1-12 years with acute uncomplicated lower respiratory tract infections. OUTCOMES: The primary outcome was the duration in days of symptoms rated moderately bad or worse (measured using a validated diary). Secondary outcomes were symptom severity on days 2-4 (0 = no problem to 6 = as bad as it could be); symptom duration until very little/no problem; reconsultations for new or worsening symptoms; complications; side effects; and resource use. METHODS: Children were randomised to receive 50 mg/kg/day of oral amoxicillin in divided doses for 7 days, or placebo using pre-prepared packs, using computer-generated random numbers by an independent statistician. Children who were not randomised could participate in a parallel observational study. Semistructured telephone interviews explored the views of 16 parents and 14 clinicians, and the data were analysed using thematic analysis. Throat swabs were analysed using multiplex polymerase chain reaction. RESULTS: A total of 432 children were randomised (antibiotics, n = 221; placebo, n = 211). The primary analysis imputed missing data for 115 children. The duration of moderately bad symptoms was similar in the antibiotic and placebo groups overall (median of 5 and 6 ...

وصف الملف: application/pdf

العلاقة: https://openaccess.sgul.ac.uk/id/eprint/115584/1/3042486.pdfTest; Little, P; Francis, NA; Stuart, B; O'Reilly, G; Thompson, N; Becque, T; Hay, AD; Wang, K; Sharland, M; Harnden, A; et al. Little, P; Francis, NA; Stuart, B; O'Reilly, G; Thompson, N; Becque, T; Hay, AD; Wang, K; Sharland, M; Harnden, A; Yao, G; Raftery, J; Zhu, S; Little, J; Hookham, C; Rowley, K; Euden, J; Harman, K; Coenen, S; Read, RC; Woods, C; Butler, CC; Faust, SN; Leydon, G; Wan, M; Hood, K; Whitehurst, J; Richards-Hall, S; Smith, P; Thomas, M; Moore, M; Verheij, T (2023) Antibiotics for lower respiratory tract infection in children presenting in primary care: ARTIC-PC RCT. Health Technol Assess, 27 (9). pp. 1-90. ISSN 2046-4924 https://doi.org/10.3310/DGBV3199Test SGUL Authors: Sharland, Michael Roy

الإتاحة: https://doi.org/10.3310/DGBV3199Test
https://openaccess.sgul.ac.uk/id/eprint/115584Test/
https://openaccess.sgul.ac.uk/id/eprint/115584/1/3042486.pdfTest

المؤلفون: Kelly, E, Greenland, M, de Whalley, PCS, Aley, PK, Plested, EL, Singh, N, Koleva, S, Tonner, S, Macaulay, GC, Read, RC, Ramsay, M, Cameron, JC, Turner, DPJ, Heath, PT, Bernatoniene, J, Connor, P, Cathie, K, Faust, SN, Banerjee, I, Cantrell, L, Mujadidi, YF, Belhadef, HT, Clutterbuck, EA, Anslow, R, Valliji, Z, James, T, Hallis, B, Otter, AD, Lambe, T, Nguyen-Van-Tam, JS, Minassian, AM, Liu, X, Snape, MD, Com-COV3 Study Group

الوصف: BACKGROUND: This was the first study to investigate the reactogenicity and immunogenicity of heterologous or fractional second dose COVID-19 vaccine regimens in adolescents. METHODS: A phase II, single-blind, multi-centre, randomised-controlled trial recruited across seven UK sites from September to November 2021, with follow-up visits to August 2022. Healthy 12-to-16 years olds were randomised (1:1:1) to either 30 µg BNT162b2 (BNT-30), 10 µg BNT162b2 (BNT-10), or NVX-CoV2373 (NVX), 8 weeks after a first 30 µg dose of BNT162b2. The primary outcome was solicited systemic reactions in the week following vaccination. Secondary outcomes included immunogenicity and safety. 'Breakthrough infection' analyses were exploratory. FINDINGS: 148 participants were recruited (median age 14 years old, 62% female, 26% anti-nucleocapsid IgG seropositive pre-second dose); 132 participants received a second dose. Reactions were mostly mild-to-moderate, with lower rates in BNT-10 recipients. No vaccine-related serious adverse events occurred. Compared to BNT-30, at 28 days post-second dose anti-spike antibody responses were similar for NVX (adjusted geometric mean ratio [aGMR]) 1.09 95% confidence interval (CI): 0.84, 1.42] and lower for BNT-10 (aGMR 0.78 [95% CI: 0.61, 0.99]). For Omicron BA.1 and BA.2, the neutralising antibody titres for BNT-30 at day 28 were similar for BNT-10 (aGMR 1.0 [95% CI: 0.65, 1.54] and 1.02 [95% CI: 0.71, 1.48], respectively), but higher for NVX (aGMR 1.7 [95% CI: 1.07, 2.69] and 1.43 [95% CI: 0.96, 2.12], respectively). Compared to BNT-30, cellular immune responses were greatest for NVX (aGMR 1.73 [95% CI: 0.94, 3.18]), and lowest for BNT-10 (aGMR 0.65 [95% CI: 0.37, 1.15]) at 14 days post-second dose. Cellular responses were similar across the study arms by day 236 post-second dose. Amongst SARS-CoV-2 infection naïve participants, NVX participants had an 89% reduction in risk of self-reported 'breakthrough infection' compared to BNT-30 (adjusted hazard ratio [aHR] 0.11 [95% CI: 0.01, 0.86]) up until ...

وصف الملف: application/pdf; application/vnd.openxmlformats-officedocument.wordprocessingml.document

العلاقة: https://openaccess.sgul.ac.uk/id/eprint/115497/7/1-s2.0-S0163445323003304-main.pdfTest; https://openaccess.sgul.ac.uk/id/eprint/115497/12/1-s2.0-S0163445323003304-mmc1.docxTest; https://openaccess.sgul.ac.uk/id/eprint/115497/1/main.pdfTest; Kelly, E; Greenland, M; de Whalley, PCS; Aley, PK; Plested, EL; Singh, N; Koleva, S; Tonner, S; Macaulay, GC; Read, RC; et al. Kelly, E; Greenland, M; de Whalley, PCS; Aley, PK; Plested, EL; Singh, N; Koleva, S; Tonner, S; Macaulay, GC; Read, RC; Ramsay, M; Cameron, JC; Turner, DPJ; Heath, PT; Bernatoniene, J; Connor, P; Cathie, K; Faust, SN; Banerjee, I; Cantrell, L; Mujadidi, YF; Belhadef, HT; Clutterbuck, EA; Anslow, R; Valliji, Z; James, T; Hallis, B; Otter, AD; Lambe, T; Nguyen-Van-Tam, JS; Minassian, AM; Liu, X; Snape, MD; Com-COV3 Study Group (2023) Reactogenicity, immunogenicity and breakthrough infections following heterologous or fractional second dose COVID-19 vaccination in adolescents (Com-COV3): A randomised controlled trial. J Infect, 87 (3). pp. 230-241. ISSN 1532-2742 https://doi.org/10.1016/j.jinf.2023.06.007Test SGUL Authors: Heath, Paul Trafford

الإتاحة: https://doi.org/10.1016/j.jinf.2023.06.007Test
https://openaccess.sgul.ac.uk/id/eprint/115497Test/
https://openaccess.sgul.ac.uk/id/eprint/115497/7/1-s2.0-S0163445323003304-main.pdfTest
https://openaccess.sgul.ac.uk/id/eprint/115497/12/1-s2.0-S0163445323003304-mmc1.docxTest
https://openaccess.sgul.ac.uk/id/eprint/115497/1/main.pdfTest

المؤلفون: Barker, C, Collet, K, Gbesemete, D, Piggin, M, Watson, D, Pristerà, P, Lawerence, W, Smith, E, Bahrami-Hessari, M, Johnson, H, Baker, K, Qavi, A, McGrath, C, Chiu, C, Read, RC, Ward, H

الوصف: Background: Human challenge studies involve the deliberate exposure of healthy volunteers to an infectious micro-organism in a highly controlled and monitored way. They are used to understand infectious diseases and have contributed to the development of vaccines. In early 2020, the UK started exploring the feasibility of establishing a human challenge study with SARS-CoV-2. Given the significant public interest and the complexity of the potential risks and benefits, it is vital that public views are considered in the design and approval of any such study and that investigators and ethics boards remain accountable to the public. Methods: Mixed methods study comprising online surveys conducted with 2,441 UK adults and in-depth virtual focus groups with 57 UK adults during October 2020 to explore the public's attitudes to a human challenge study with SARS-CoV-2 taking place in the UK. Results: There was overall agreement across the surveys and focus groups that a human challenge study with SARS-CoV-2 should take place in the UK. Transparency of information, trust and the necessity to provide clear information on potential risks to study human challenge study participants were important. The perceived risks of taking part included the risk of developing long-term effects from COVID, impact on personal commitments and mental health implications of isolation. There were a number of practical realities to taking part that would influence a volunteer's ability to participate (e.g. Wi-Fi, access to exercise, outside space and work, family and pet commitments). Conclusions: The results identified practical considerations for teams designing human challenge studies. Recommendations were grouped: 1) messaging to potential study participants, 2) review of the protocol and organisation of the study, and 3) more broadly, making the study more inclusive and relevant. This study highlights the value of public consultation in research, particularly in fields attracting public interest and scrutiny .

العلاقة: Barker, C., Collet, K., Gbesemete, D., Piggin, M., Watson, D., Pristerà, P., Lawerence, W., Smith, E., Bahrami-Hessari, M., Johnson, H., Baker, K., Qavi, A., McGrath, C., Chiu, C., Read, R. C. & Ward, H. (2022). Public attitudes to a human challenge study with SARS-CoV-2: a mixed-methods study. Wellcome Open Res, 7, pp.49-. https://doi.org/10.12688/wellcomeopenres.17516.1Test.; http://hdl.handle.net/11343/316873Test

الإتاحة: https://doi.org/10.12688/wellcomeopenres.17516.1Test
http://hdl.handle.net/11343/316873Test

المؤلفون: Piggin, M, Smith, E, Mankone, P, Ndegwa, L, Gbesemete, D, Pristerà, P, Bahrami-Hessari, M, Johnson, H, Catchpole, AP, Openshaw, PJM, Chiu, C, Read, RC, Ward, H, Barker, C

الوصف: High quality health care research must involve patients and the public. This ensures research is important, relevant and acceptable to those it is designed to benefit. The world's first human challenge study with SARS-CoV-2 undertook detailed public involvement to inform study design despite the urgency to review and establish the study. The work was integral to the UK Research Ethics Committee review and approval of the study. Discussion with individuals from ethnic minorities within the UK population supported decision-making around the study exclusion criteria. Public review of study materials for consent processes led to the addition of new information, comparisons and visual aids to help volunteers consider the practicalities and risks involved in participating. A discussion exploring the acceptability of a human challenge study with SARS-CoV-2 taking place in the UK, given the current context of the pandemic, identified overall support for the study. Public concern for the wellbeing of trial participants, as a consequence of isolation, was identified. We outline our approach to public involvement and its impact on study design.

العلاقة: pii: S1755-4365(22)00066-4; Piggin, M., Smith, E., Mankone, P., Ndegwa, L., Gbesemete, D., Pristerà, P., Bahrami-Hessari, M., Johnson, H., Catchpole, A. P., Openshaw, P. J. M., Chiu, C., Read, R. C., Ward, H. & Barker, C. (2022). The role of public involvement in the design of the first SARS-CoV-2 human challenge study during an evolving pandemic. Epidemics, 41, pp.100626-. https://doi.org/10.1016/j.epidem.2022.100626Test.; http://hdl.handle.net/11343/335867Test

الإتاحة: https://doi.org/10.1016/j.epidem.2022.100626Test
http://hdl.handle.net/11343/335867Test

المؤلفون: Liu, X, Munro, APS, Feng, S, Janani, L, Aley, PK, Babbage, G, Baxter, D, Bula, M, Cathie, K, Chatterjee, K, Dejnirattisai, W, Dodd, K, Enever, Y, Qureshi, E, Goodman, AL, Green, CA, Harndahl, L, Haughney, J, Hicks, A, van der Klaauw, AA, Kwok, J, 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, Serafimova, T, Saralaya, D, Screaton, GR, Sharma, S, Sheridan, R, Sturdy, A, Supasa, P, Thomson, EC, Todd, S, Twelves, C, Read, RC, Charlton, S, Hallis, B, Ramsay, M, Andrews, N, Lambe, T, Nguyen-Van-Tam, JS, Cornelius, V, Snape, MD, Faust, SN

المساهمون: group, COV-BOOST study

الوصف: OBJECTIVES: To evaluate the persistence of immunogenicity three months after third dose boosters. METHODS: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose. The analysis was conducted using all randomised participants who were SARS-CoV-2 naïve during the study. RESULTS: Amongst the 2883 participants randomised, there were 2422 SARS-CoV-2 naïve participants until D84 visit included in the analysis with median age of 70 (IQR: 30–94) years. In the participants who had two initial doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd), schedules using mRNA vaccines as third dose have the highest anti-spike IgG at D84 (e.g. geometric mean concentration of 8674 ELU/ml (95% CI: 7461–10,085) following ChAd/ChAd/BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT)). However, in people who had two initial doses of BNT there was no significant difference at D84 in people given ChAd versus BNT (geometric mean ratio (GMR) of 0.95 (95%CI: 0.78, 1.15). Also, people given Ad26.COV2.S (Janssen; hereafter referred to as Ad26) as a third dose had significantly higher anti-spike IgG at D84 than BNT (GMR of 1.20, 95%CI: 1.01,1.43). Responses at D84 between people who received BNT (15 μg) or BNT (30 μg) after ChAd/ChAd or BNT/BNT were similar, with anti-spike IgG GMRs of half-BNT (15 μg) versus BNT (30 μg) ranging between 0.74–0.86. The decay rate of cellular responses were similar between all the vaccine schedules and doses. CONCLUSIONS: 84 days after a third dose of COVID-19 vaccine the decay rates of humoral response were different between vaccines. Adenoviral vector vaccine anti-spike IgG concentrations at D84 following BNT/BNT initial doses were similar to or even higher than for a three dose (BNT/BNT/BNT) schedule. Half dose BNT immune responses were similar to full dose responses. While high antibody tires are desirable in situations of high transmission of new variants of concern, the maintenance of immune responses that confer ...

العلاقة: https://ora.ox.ac.uk/objects/uuid:ed9915c6-089f-4b60-9d48-38c8018eea79Test; https://doi.org/10.1016/j.jinf.2022.04.018Test

الإتاحة: https://doi.org/10.1016/j.jinf.2022.04.018Test
https://ora.ox.ac.uk/objects/uuid:ed9915c6-089f-4b60-9d48-38c8018eea79Test

المؤلفون: Shaw, RH, Liu, X, Stuart, ASV, Greenland, M, Aley, PK, Andrews, NJ, Cameron, JC, Charlton, S, Clutterbuck, EA, Collins, AM, Dejnirattisai, W, Dinesh, T, Faust, SN, Ferreira, DM, Finn, A, Green, CA, Hallis, B, Heath, PT, Hill, H, Lambe, T, Lazarus, R, Libri, V, Long, F, Mujadidi, YF, Plested, EL, Morey, ER, Provstgaard-Morys, S, Ramasamy, MN, Ramsay, M, Read, RC, Robinson, H, Screaton, GR, Singh, N, Turner, DPJ, Turner, PJ, Vichos, I, Walker, LL, White, R, Nguyen-Van-Tam, JS, Snape, MD

المساهمون: Group, Com-COV Study

الوصف: Background Priming COVID-19 vaccine schedules have been deployed at variable intervals globally, which might influence immune persistence and the relative importance of third-dose booster programmes. Here, we report exploratory analyses from the Com-COV trial, assessing the effect of 4-week versus 12-week priming intervals on reactogenicity and the persistence of immune response up to 6 months after homologous and heterologous priming schedules using the vaccines BNT162b2 (tozinameran, Pfizer/BioNTech) and ChAdOx1 nCoV-19 (AstraZeneca). Methods Com-COV was a participant-masked, randomised immunogenicity trial. For these exploratory analyses, we used the trial's general cohort, in which adults aged 50 years or older were randomly assigned to four homologous and four heterologous vaccine schedules using BNT162b2 and ChAdOx1 nCoV-19 with 4-week or 12-week priming intervals (eight groups in total). Immunogenicity analyses were done on the intention-to-treat (ITT) population, comprising participants with no evidence of SARS-CoV-2 infection at baseline or for the trial duration, to assess the effect of priming interval on humoral and cellular immune response 28 days and 6 months post-second dose, in addition to the effects on reactogenicity and safety. The Com-COV trial is registered with the ISRCTN registry, 69254139 (EudraCT 2020–005085–33). Findings Between Feb 11 and 26, 2021, 730 participants were randomly assigned in the general cohort, with 77–89 per group in the ITT analysis. At 28 days and 6 months post-second dose, the geometric mean concentration of anti-SARS-CoV-2 spike IgG was significantly higher in the 12-week interval groups than in the 4-week groups for homologous schedules. In heterologous schedule groups, we observed a significant difference between intervals only for the BNT162b2–ChAdOx1 nCoV-19 group at 28 days. Pseudotyped virus neutralisation titres were significantly higher in all 12-week interval groups versus 4-week groups, 28 days post-second dose, with geometric mean ratios of 1·4 (95% CI ...

العلاقة: https://ora.ox.ac.uk/objects/uuid:873e54e6-4030-4c8e-a474-91d91769325eTest; https://doi.org/10.1016/s2213-2600Test(22)00163-1

الإتاحة: https://doi.org/10.1016/s2213-2600Test(22)00163-1
https://ora.ox.ac.uk/objects/uuid:873e54e6-4030-4c8e-a474-91d91769325eTest

المؤلفون: Stuart, ASV, Shaw, RH, Liu, X, Greenland, M, Aley, PK, Andrews, NJ, Cameron, JC, Charlton, S, Clutterbuck, EA, Collins, AM, Darton, T, Dinesh, T, Duncan, CJA, England, A, Faust, SN, Ferreira, DM, Finn, A, Goodman, AL, Green, CA, Hallis, B, Heath, PT, Hill, H, Horsington, BM, Lambe, T, Lazarus, R, Libri, V, Lillie, PJ, Mujadidi, YF, Payne, R, Plested, EL, Provstgaard-Morys, S, Ramasamy, MN, Ramsay, M, Read, RC, Robinson, H, Screaton, GR, Singh, N, Turner, DPJ, Turner, PJ, Vichos, I, White, R, Nguyen-Van-Tam, JS, Snape, MD

المساهمون: Group, Com-COV2 Study

الوصف: Background Given the importance of flexible use of different COVID-19 vaccines within the same schedule to facilitate rapid deployment, we studied mixed priming schedules incorporating an adenoviral-vectored vaccine (ChAdOx1 nCoV-19 [ChAd], AstraZeneca), two mRNA vaccines (BNT162b2 [BNT], Pfizer–BioNTech, and mRNA-1273 [m1273], Moderna) and a nanoparticle vaccine containing SARS-CoV-2 spike glycoprotein and Matrix-M adjuvant (NVX-CoV2373 [NVX], Novavax). Methods Com-COV2 is a single-blind, randomised, non-inferiority trial in which adults aged 50 years and older, previously immunised with a single dose of ChAd or BNT in the community, were randomly assigned (in random blocks of three and six) within these cohorts in a 1:1:1 ratio to receive a second dose intramuscularly (8–12 weeks after the first dose) with the homologous vaccine, m1273, or NVX. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentrations measured by ELISA in heterologous versus homologous schedules at 28 days after the second dose, with a non-inferiority criterion of the GMR above 0·63 for the one-sided 98·75% CI. The primary analysis was on the per-protocol population, who were seronegative at baseline. Safety analyses were done for all participants who received a dose of study vaccine. The trial is registered with ISRCTN, number 27841311. Findings Between April 19 and May 14, 2021, 1072 participants were enrolled at a median of 9·4 weeks after receipt of a single dose of ChAd (n=540, 47% female) or BNT (n=532, 40% female). In ChAd-primed participants, geometric mean concentration (GMC) 28 days after a boost of SARS-CoV-2 anti-spike IgG in recipients of ChAd/m1273 (20 114 ELISA laboratory units [ELU]/mL [95% CI 18 160 to 22 279]) and ChAd/NVX (5597 ELU/mL [4756 to 6586]) was non-inferior to that of ChAd/ChAd recipients (1971 ELU/mL [1718 to 2262]) with a GMR of 10·2 (one-sided 98·75% CI 8·4 to ∞) for ChAd/m1273 and 2·8 (2·2 to ∞) for ChAd/NVX, compared with ChAd/ChAd. In BNT-primed participants, ...

العلاقة: https://ora.ox.ac.uk/objects/uuid:da01cb4e-98ba-4417-b888-9832a907d5feTest; https://doi.org/10.1016/s0140-6736Test(21)02718-5

الإتاحة: https://doi.org/10.1016/s0140-6736Test(21)02718-5
https://ora.ox.ac.uk/objects/uuid:da01cb4e-98ba-4417-b888-9832a907d5feTest

المؤلفون: Liu, X, Shaw, RH, Stuart, ASV, Greenland, M, Aley, PK, Andrews, NJ, Cameron, JC, Charlton, S, Clutterbuck, EA, Collins, AM, Dinesh, T, England, A, Faust, SN, Ferreira, DM, Finn, A, Green, CA, Hallis, B, Heath, PT, Hill, H, Lambe, T, Lazarus, R, Libri, V, Long, F, Mujadidi, YF, Plested, EL, Provstgaard-Morys, S, Ramasamy, MN, Ramsay, M, Read, RC, Robinson, H, Singh, N, Turner, DPJ, Turner, PJ, Walker, LL, White, R, Nguyen-Van-Tam, JS, Snape, MD

المساهمون: Group, Com-COV Study

الوصف: Background Use of heterologous prime-boost COVID-19 vaccine schedules could facilitate mass COVID-19 immunisation. However, we have previously reported that heterologous schedules incorporating an adenoviral vectored vaccine (ChAdOx1 nCoV-19, AstraZeneca; hereafter referred to as ChAd) and an mRNA vaccine (BNT162b2, Pfizer–BioNTech; hereafter referred to as BNT) at a 4-week interval are more reactogenic than homologous schedules. Here, we report the safety and immunogenicity of heterologous schedules with the ChAd and BNT vaccines. Methods Com-COV is a participant-blinded, randomised, non-inferiority trial evaluating vaccine safety, reactogenicity, and immunogenicity. Adults aged 50 years and older with no or well controlled comorbidities and no previous SARS-CoV-2 infection by laboratory confirmation were eligible and were recruited at eight sites across the UK. The majority of eligible participants were enrolled into the general cohort (28-day or 84-day prime-boost intervals), who were randomly assigned (1:1:1:1:1:1:1:1) to receive ChAd/ChAd, ChAd/BNT, BNT/BNT, or BNT/ChAd, administered at either 28-day or 84-day prime-boost intervals. A small subset of eligible participants (n=100) were enrolled into an immunology cohort, who had additional blood tests to evaluate immune responses; these participants were randomly assigned (1:1:1:1) to the four schedules (28-day interval only). Participants were masked to the vaccine received but not to the prime-boost interval. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentration (measured by ELISA) at 28 days after boost, when comparing ChAd/BNT with ChAd/ChAd, and BNT/ChAd with BNT/BNT. The heterologous schedules were considered non-inferior to the approved homologous schedules if the lower limit of the one-sided 97·5% CI of the GMR of these comparisons was greater than 0·63. The primary analysis was done in the per-protocol population, who were seronegative at baseline. Safety analyses were done among participants ...

العلاقة: https://ora.ox.ac.uk/objects/uuid:63375656-55a9-464c-8a96-60a2565fd45cTest; https://doi.org/10.1016/s0140-6736Test(21)01694-9

الإتاحة: https://doi.org/10.1016/s0140-6736Test(21)01694-9
https://ora.ox.ac.uk/objects/uuid:63375656-55a9-464c-8a96-60a2565fd45cTest