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; M Dymock; K L Flanagan; M Plebanski; H Marshall; M J Estcourt; M C Tjiam; C C Blyth; K Subbarao; F L Mordant; S Nicholson; S N Faust; U Wadia; R B Thornton; Z Ellis; A Mckenzie; J A Marsh; T L Snelling; P Richmond

doi:10.1016/j.jinf.2024.106286

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

J Infect. 2024 Sep 26;89(6):106286. doi: 10.1016/j.jinf.2024.106286. Online ahead of print.

Authors

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

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.