Your browser doesn't support javascript.
loading
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.
Nolan, Terry M; Deliyannis, Georgia; Griffith, Maryanne; Braat, Sabine; Allen, Lilith F; Audsley, Jennifer; Chung, Amy W; Ciula, Marcin; Gherardin, Nicholas A; Giles, Michelle L; Gordon, Tom P; Grimley, Samantha L; Horng, Lana; Jackson, David C; Juno, Jennifer A; Kedzierska, Katherine; Kent, Stephen J; Lewin, Sharon R; Littlejohn, Mason; McQuilten, Hayley A; Mordant, Francesca L; Nguyen, Thi H O; Soo, Vanessa Pac; Price, Briony; Purcell, Damian F J; Ramanathan, Pradhipa; Redmond, Samuel J; Rockman, Steven; Ruan, Zheng; Sasadeusz, Joseph; Simpson, Julie A; Subbarao, Kanta; Fabb, Stewart A; Payne, Thomas J; Takanashi, Asuka; Tan, Chee Wah; Torresi, Joseph; Wang, Jing Jing; Wang, Lin-Fa; Al-Wassiti, Hareth; Wong, Chinn Yi; Zaloumis, Sophie; Pouton, Colin W; Godfrey, Dale I.
Afiliación
  • Nolan TM; Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Australia; Murdoch Children's Research Institute, Melbourne, Australia. Electronic address: t.nolan@unimelb.edu.au.
  • Deliyannis G; Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
  • Griffith M; Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Australia.
  • Braat S; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
  • Allen LF; Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
  • Audsley J; Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
  • Chung AW; Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
  • Ciula M; Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
  • Gherardin NA; Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
  • Giles ML; Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Australia.
  • Gordon TP; Department of Immunology, Flinders University and SA Pathology, Flinders Medical Centre, Bedford Park, Adelaide, Australia.
  • Grimley SL; Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
  • Horng L; Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Australia; Murdoch Children's Research Institute, Melbourne, Australia.
  • Jackson DC; Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
  • Juno JA; Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
  • Kedzierska K; Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo, Japan.
  • Kent SJ; Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
  • Lewin SR; Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Australia; Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; Department of
  • Littlejohn M; Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Australia.
  • McQuilten HA; Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
  • Mordant FL; Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
  • Nguyen THO; Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
  • Soo VP; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
  • Price B; Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Australia; Murdoch Children's Research Institute, Melbourne, Australia.
  • Purcell DFJ; Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
  • Ramanathan P; Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
  • Redmond SJ; Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
  • Rockman S; Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; CSL Seqirus, Vaccine Innovation Unit, Parkville, Melbourne, Australia.
  • Ruan Z; Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
  • Sasadeusz J; Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia.
  • Simpson JA; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
  • Subbarao K; Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Australia.
  • Fabb SA; Monash Institute of Pharmaceutical Sciences, Parkville, Australia.
  • Payne TJ; Monash Institute of Pharmaceutical Sciences, Parkville, Australia.
  • Takanashi A; Monash Institute of Pharmaceutical Sciences, Parkville, Australia.
  • Tan CW; Duke NUS Medical School, Programme for Emerging Infectious Diseases, Singapore.
  • Torresi J; Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
  • Wang JJ; Department of Immunology, Flinders University and SA Pathology, Flinders Medical Centre, Bedford Park, Adelaide, Australia.
  • Wang LF; Duke NUS Medical School, Programme for Emerging Infectious Diseases, Singapore.
  • Al-Wassiti H; Monash Institute of Pharmaceutical Sciences, Parkville, Australia.
  • Wong CY; Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
  • Zaloumis S; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
  • Pouton CW; Monash Institute of Pharmaceutical Sciences, Parkville, Australia.
  • Godfrey DI; Department of Microbiology & Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
EBioMedicine ; 98: 104878, 2023 Dec.
Article en En | MEDLINE | ID: mdl-38016322
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®, 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 govNCT05272605.

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.
Asunto(s)
Palabras clave
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Vacunas contra la COVID-19 / COVID-19 Límite: Adolescent / Adult / Humans / Middle aged País/Región como asunto: Oceania Idioma: En Revista: EBioMedicine Año: 2023 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Vacunas contra la COVID-19 / COVID-19 Límite: Adolescent / Adult / Humans / Middle aged País/Región como asunto: Oceania Idioma: En Revista: EBioMedicine Año: 2023 Tipo del documento: Article