@article{831aa685c4d84bc9ab3735b7d792b0f0,
title = "Interim results from a phase I randomized, placebo-controlled trial of novel SARS-CoV-2 beta variant receptor-binding domain recombinant protein and mRNA vaccines as a 4th dose booster",
abstract = "Background: SARS-CoV-2 booster vaccination should ideally enhance protection against variants and minimise immune imprinting. This Phase I trial evaluated two vaccines targeting SARS-CoV-2 beta-variant receptor-binding domain (RBD): a recombinant dimeric RBD-human IgG1 Fc-fusion protein, and an mRNA encoding a membrane-anchored RBD. Methods: 76 healthy adults aged 18–64 y, previously triple vaccinated with licensed SARS-CoV-2 vaccines, were randomised to receive a 4th dose of either an adjuvanted (MF59{\textregistered}, CSL Seqirus) protein vaccine (5, 15 or 45 μg, N = 32), mRNA vaccine (10, 20, or 50 μg, N = 32), or placebo (saline, N = 12) at least 90 days after a 3rd boost vaccination or SARS-CoV-2 infection. Bleeds occurred on days 1 (prior to vaccination), 8, and 29. ClinicalTrials.gov NCT05272605. Findings: No vaccine-related serious or medically-attended adverse events occurred. The protein vaccine reactogenicity was mild, whereas the mRNA vaccine was moderately reactogenic at higher dose levels. Best anti-RBD antibody responses resulted from the higher doses of each vaccine. A similar pattern was seen with live virus neutralisation and surrogate, and pseudovirus neutralisation assays. Breadth of immune response was demonstrated against BA.5 and more recent omicron subvariants (XBB, XBB.1.5 and BQ.1.1). Binding antibody titres for both vaccines were comparable to those of a licensed bivalent mRNA vaccine. Both vaccines enhanced CD4+ and CD8+ T cell activation. Interpretation: There were no safety concerns and the reactogenicity profile was mild and similar to licensed SARS-CoV-2 vaccines. Both vaccines showed strong immune boosting against beta, ancestral and omicron strains. Funding: Australian Government Medical Research Future Fund, and philanthropies Jack Ma Foundation and IFM investors.",
keywords = "Beta variant, mRNA, Phase I trial, Receptor binding domain, Recombinant protein, SARS-CoV-2, Vaccine",
author = "Nolan, {Terry M.} and Georgia Deliyannis and Maryanne Griffith and Sabine Braat and Allen, {Lilith F.} and Jennifer Audsley and Chung, {Amy W.} and Marcin Ciula and Gherardin, {Nicholas A.} and Giles, {Michelle L.} and Gordon, {Tom P.} and Grimley, {Samantha L.} and Lana Horng and Jackson, {David C.} and Juno, {Jennifer A.} and Katherine Kedzierska and Kent, {Stephen J.} and Lewin, {Sharon R.} and Mason Littlejohn and McQuilten, {Hayley A.} and Mordant, {Francesca L.} and Nguyen, {Thi H.O.} and Soo, {Vanessa Pac} and Briony Price and Purcell, {Damian F.J.} and Pradhipa Ramanathan and Redmond, {Samuel J.} and Steven Rockman and Zheng Ruan and Joseph Sasadeusz and Simpson, {Julie A.} and Kanta Subbarao and Fabb, {Stewart A.} and Payne, {Thomas J.} and Asuka Takanashi and Tan, {Chee Wah} and Joseph Torresi and Wang, {Jing Jing} and Wang, {Lin Fa} and Hareth Al-Wassiti and Wong, {Chinn Yi} and Sophie Zaloumis and Pouton, {Colin W.} and Godfrey, {Dale I.}",
note = "Funding Information: Australian Government Medical Research Future Fund, and philanthropies Jack Ma Foundation and IFM investors.The authors wish to thank all the study volunteer participants. We acknowledge VIRGo research nurses and doctors: Lani Shiels, Janet Briggs, Clare Brophy, Megan Hocking, Annmarie McEvoy, Dima El Sukkari, and Marita Nolan; Royal Melbourne Hospital (RMH) research nurse Joanne Patterson in the lower dose sentinel stage; Hayley Page and Helen Kent (Kent group); RMH Pharmacy (Clinical Trials Group) who managed study IP; staff of Southern Star Research who were contracted to act as the CRO for data management and monitoring. We thank our COVID Vaccine Advisory Panel: Manon Cox, Peter Dull, John McEwen, Kim Wright, and Mike Levine. Additional scientific and regulatory advice was provided by Mark Sullivan, Jim Ackland, James McCluskey, and Gary Grohmann. We thank DSMB members Jim Buttery, Jo-Anne Grey, Sue Lee, and Peter Richmond. Many others provided valuable input into vaccine manufacture, quality assurance, documentation: Trent Munro (University of Queensland) and Jillian Bennet (Tanawell Consulting); from CSIRO Judith Scoble, John Power, Pat Pilling, Susie Nilsson, and Tram Phan; Drew Brockman and Peter Tapley (Agilex Biolabs); Marianne Gillard, Kym Hoger, Karen Hughes, Ben Hughes, Martina Jones, Paul Young and Keith Chappell (University of Queensland); Lena Miloradovic, Jenny Herz, Fiona Seddon, Denison Chang and Patricia Vietheer (Biointelect). We acknowledge provision of facilities, and scientific and technical assistance of the National Biologics Facility (NBF) whose University of Queensland node and CSIRO node are supported by Therapeutic Innovation Australia (TIA), and the Australian Government through the National Collaborative Research Infrastructure Strategy program. We thank CSL Seqirus for donating the MF59{\textregistered} adjuvant. Funding: Medical Research Future Fund (MRFF) Awards (2005990, 2005846, 2005544), The Jack Ma Foundation, and National Health and Medical Research Council of Australia (NHMRC; 2008913, 1173871, 1194036) and mRNA Victoria. Philanthropic funds from IFM Investors. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health. Duke-NUS supported by Singapore National Medical Research Council (MOH-COVID19RF-003). Funding Information: Funding: Medical Research Future Fund (MRFF) Awards ( 2005990 , 2005846 , 2005544 ), The Jack Ma Foundation , and National Health and Medical Research Council of Australia (NHMRC; 2008913 , 1173871 , 1194036 ) and mRNA Victoria. Philanthropic funds from IFM Investors. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health . Duke-NUS supported by Singapore National Medical Research Council (MOH-COVID19RF-003). Funding Information: Many others provided valuable input into vaccine manufacture, quality assurance, documentation: Trent Munro (University of Queensland) and Jillian Bennet (Tanawell Consulting); from CSIRO Judith Scoble, John Power, Pat Pilling, Susie Nilsson, and Tram Phan; Drew Brockman and Peter Tapley (Agilex Biolabs); Marianne Gillard, Kym Hoger, Karen Hughes, Ben Hughes, Martina Jones, Paul Young and Keith Chappell (University of Queensland); Lena Miloradovic, Jenny Herz, Fiona Seddon, Denison Chang and Patricia Vietheer (Biointelect). We acknowledge provision of facilities, and scientific and technical assistance of the National Biologics Facility (NBF) whose University of Queensland node and CSIRO node are supported by Therapeutic Innovation Australia (TIA), and the Australian Government through the National Collaborative Research Infrastructure Strategy program. We thank CSL Seqirus for donating the MF59{\textregistered} adjuvant. Publisher Copyright: {\textcopyright} 2023 The Author(s)",
year = "2023",
month = dec,
doi = "10.1016/j.ebiom.2023.104878",
language = "English",
volume = "98",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "The Lancet Publishing Group",
}