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

Terry M. Nolan, Georgia Deliyannis, Maryanne Griffith, Sabine Braat, Lilith F. Allen, Jennifer Audsley, Amy W. Chung, Marcin Ciula, Nicholas A. Gherardin, Michelle L. Giles, Tom P. Gordon, Samantha L. Grimley, Lana Horng, David C. Jackson, Jennifer A. Juno, Katherine Kedzierska, Stephen J. Kent, Sharon R. Lewin, Mason Littlejohn, Hayley A. McQuiltenFrancesca L. Mordant, Thi H.O. Nguyen, Vanessa Pac Soo, Briony Price, Damian F.J. Purcell, Pradhipa Ramanathan, Samuel J. Redmond, Steven Rockman, Zheng Ruan, Joseph Sasadeusz, Julie A. Simpson, Kanta Subbarao, Stewart A. Fabb, Thomas J. Payne, Asuka Takanashi, Chee Wah Tan, Joseph Torresi, Jing Jing Wang, Lin-Fa Wang, Hareth Al-Wassiti, Chinn Yi Wong, Sophie Zaloumis, Colin W. Pouton, Dale I. Godfrey

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
25 Downloads (Pure)

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 IgG 1 F c-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®, 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.

Original languageEnglish
Article number104878
Number of pages17
JournalEBioMedicine
Volume98
Early online date27 Nov 2023
DOIs
Publication statusPublished - Dec 2023

Keywords

  • SARS-CoV-2
  • Vaccine
  • Receptor binding domain
  • Recombinant protein
  • mRNA
  • Beta variant
  • Phase I trial

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this