The Platform Trial In COVID-19 Priming and BOOsting (PICOBOO): The immunogenicity, reactogenicity, and safety of different COVID-19 vaccinations administered as a second booster (fourth dose) in AZD1222 primed individuals aged 50-<70 years old

C McLeod¹, M Dymock², K L Flanagan³, M Plebanski⁴, H Marshall⁵, M J Estcourt⁶, M C Tjiam², C C Blyth⁷, K Subbarao⁸, F L Mordant⁹, S Nicholson¹⁰, S N Faust¹¹, U Wadia¹², R B Thornton², Z Ellis², A Mckenzie², J A Marsh¹³, T L Snelling⁶, P Richmond¹⁴

Affiliations

¹ Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Australia; Infectious Diseases Department, Perth Children's Hospital, Nedlands, Australia; School of Medicine, University of Western Australia, Crawley, Australia. Electronic address: charlie.mcleod@health.wa.gov.au.
² Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Australia.
³ Tasmanian Vaccine Trial Centre, Clifford Craig Foundation, Launceston General Hospital, Tasmania, Australia; School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, Tasmania, Australia; School of Health and Biomedical Sciences, Royal Melbourne Institute of Technology University (RMIT), Melbourne, Australia.
⁴ School of Health and Biomedical Sciences, Royal Melbourne Institute of Technology University (RMIT), Melbourne, Australia.
⁵ Women's and Children's Health Network, North Adelaide, Australia; Robinson Research Institute and Adelaide Medical School, The University of Adelaide, Australia.
⁶ Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Australia.
⁷ Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Australia; Infectious Diseases Department, Perth Children's Hospital, Nedlands, Australia; School of Medicine, University of Western Australia, Crawley, Australia; Department of Microbiology, Pathwest Laboratory Medicine WA, QEII Medical Centre, Nedlands, Australia.
⁸ WHO Collaborating Centre for Reference and Research on Influenza, University of Melbourne, Parkville, Victoria, Australia; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
⁹ Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
¹⁰ Victorian Infectious Diseases Reference Laboratory, The Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
¹¹ National Institute of Health Research Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; Faculty of Medicine and Institute for Life Sciences, University of Southampton, United Kingdom.
¹² Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Australia; Infectious Diseases Department, Perth Children's Hospital, Nedlands, Australia; Centre for Child Health Research, University of Western Australia, Crawley, Australia.
¹³ Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Australia; School of Medicine, University of Western Australia, Crawley, Australia.
¹⁴ Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Australia; School of Medicine, University of Western Australia, Crawley, Australia; Centre for Child Health Research, University of Western Australia, Crawley, Australia; General Paediatrics and Immunology Departments, Perth Children's Hospital, Nedlands, Australia.

PMID: 39341401
DOI: 10.1016/j.jinf.2024.106286

Free article

Randomized Controlled Trial

The Platform Trial In COVID-19 Priming and BOOsting (PICOBOO): The immunogenicity, reactogenicity, and safety of different COVID-19 vaccinations administered as a second booster (fourth dose) in AZD1222 primed individuals aged 50-<70 years old

C McLeod et al. J Infect. 2024 Dec.

Free article

. 2024 Dec;89(6):106286.

doi: 10.1016/j.jinf.2024.106286. Epub 2024 Sep 26.

Authors

Affiliations

¹ Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Australia; Infectious Diseases Department, Perth Children's Hospital, Nedlands, Australia; School of Medicine, University of Western Australia, Crawley, Australia. Electronic address: charlie.mcleod@health.wa.gov.au.
² Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Australia.
³ Tasmanian Vaccine Trial Centre, Clifford Craig Foundation, Launceston General Hospital, Tasmania, Australia; School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, Tasmania, Australia; School of Health and Biomedical Sciences, Royal Melbourne Institute of Technology University (RMIT), Melbourne, Australia.
⁴ School of Health and Biomedical Sciences, Royal Melbourne Institute of Technology University (RMIT), Melbourne, Australia.
⁵ Women's and Children's Health Network, North Adelaide, Australia; Robinson Research Institute and Adelaide Medical School, The University of Adelaide, Australia.
⁶ Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Australia.
⁷ Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Australia; Infectious Diseases Department, Perth Children's Hospital, Nedlands, Australia; School of Medicine, University of Western Australia, Crawley, Australia; Department of Microbiology, Pathwest Laboratory Medicine WA, QEII Medical Centre, Nedlands, Australia.
⁸ WHO Collaborating Centre for Reference and Research on Influenza, University of Melbourne, Parkville, Victoria, Australia; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
⁹ Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
¹⁰ Victorian Infectious Diseases Reference Laboratory, The Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
¹¹ National Institute of Health Research Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom; Faculty of Medicine and Institute for Life Sciences, University of Southampton, United Kingdom.
¹² Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Australia; Infectious Diseases Department, Perth Children's Hospital, Nedlands, Australia; Centre for Child Health Research, University of Western Australia, Crawley, Australia.
¹³ Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Australia; School of Medicine, University of Western Australia, Crawley, Australia.
¹⁴ Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, Australia; School of Medicine, University of Western Australia, Crawley, Australia; Centre for Child Health Research, University of Western Australia, Crawley, Australia; General Paediatrics and Immunology Departments, Perth Children's Hospital, Nedlands, Australia.

PMID: 39341401
DOI: 10.1016/j.jinf.2024.106286

Abstract

Objectives: PICOBOO is a randomised, adaptive trial evaluating the immunogenicity, reactogenicity, and safety of COVID-19 booster strategies. We report data for second boosters among individuals 50-<70 years old primed with AZD1222 (50-<70y-AZD1222) until Day 84.

Methods: Immunocompetent adults who received any first booster ≥three months prior were eligible. Participants were randomly allocated to BNT162b2, mRNA-1273 or NVX-CoV2373 1:1:1. The concentrations of ancestral anti-spike immunoglobulin were summarised as the geometric mean concentrations (GMC). Reactogenicity and safety outcomes were captured. Additional analyses including neutralising antibodies were performed on a subset. ACTRN12622000238774.

Results: Between Mar 2022 and Aug 2023, 743 participants were recruited and had D28 samples; 155 belonged to the 50-<70y-AZD1222 stratum. The mean adjusted GMCs (95% credible intervals) were 20,690 (17 555-23 883), 23,867 (20 144-27 604) and 8654 (7267-9962) U/mL at D28 following boosting with BNT162b2, mRNA-1273 and NVX-CoV2372, respectively, and 10,976 (8826-13 196), 15,779 (12 512-19 070) and 6559 (5220-7937) U/mL by D84. IgG against Omicron BA.5 was 2.7-2.9 times lower than the ancestral strain. Limited neutralisation against Omicron subvariants was found following all vaccines. Severe reactogenicity events were <4%.

Conclusions: All vaccines were immunogenic with more rapid waning after mRNA vaccines. These data support boosting with vaccines with greater specificity for circulating Omicron subvariants.

Keywords: Adaptive trial; COVID-19; Immunisation; Policy.

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Conflict of interest statement

Declaration of Competing Interest KF and TS are members of the Australian Technical Advisory Group on Immunisation (ATAGI), which advises the government on vaccine policy; their involvement as investigators on this trial has been declared to ATAGI. MP is involved in an ovarian cancer clinical trial that received funding from AstraZeneca. MP was involved in performing immunological assays on biological specimens obtained from participants in this trial, but was not involved in participant recruitment, data collection or the analysis of results. SNF leads the UK National Institute for Health and Care Research funded trial of third and fourth-dose COVID-19 boosters. SNF acts on behalf of University Hospital Southampton NHS Foundation Trust, UK, as an Investigator and/or providing consultative advice on clinical trials and studies of vaccines funded or sponsored by vaccine manufacturers including Moderna, Sanofi, Janssen, Pfizer, AstraZeneca, GlaxoSmithKline, Novavax, Seqirus, Medimmune, Merck and Valneva vaccines and antimicrobials. UW is an investigator on clinical trials of vaccines funded or sponsored by vaccine manufactures including Moderna, Sanofi, Pfizer, Merck and GlaxoSmithKline. PR also reports acting on behalf of University of Western Australia, as an Investigator and/or providing consultative advice on clinical trials and studies of vaccines funded or sponsored by vaccine manufacturers including Moderna, Sanofi, Janssen, Pfizer, AstraZeneca, GlaxoSmithKline, Novavax, Seqirus, Merck and Clover Biopharmaceutical vaccines. They receive no personal financial payment for this work. The other authors declare that they have no competing interests.

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The Platform Trial In COVID-19 Priming and BOOsting (PICOBOO): The immunogenicity, reactogenicity, and safety of different COVID-19 vaccinations administered as a second booster (fourth dose) in AZD1222 primed individuals aged 50-<70 years old

Affiliations

The Platform Trial In COVID-19 Priming and BOOsting (PICOBOO): The immunogenicity, reactogenicity, and safety of different COVID-19 vaccinations administered as a second booster (fourth dose) in AZD1222 primed individuals aged 50-<70 years old

Authors

Affiliations

Abstract

Conflict of interest statement

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Full Text Sources

Medical