First-in-human use of a modular capsid virus-like vaccine platform: an open-label, non-randomised, phase 1 clinical trial of the SARS-CoV-2 vaccine ABNCoV2.

Autor:	Smit MJ; Department of Medical Microbiology, Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands; Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands., Sander AF; AdaptVac Aps, Copenhagen, Denmark; Centre for Medical Parasitology, Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Ariaans MBPA; Department of Medical Microbiology, Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands; Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands., Fougeroux C; AdaptVac Aps, Copenhagen, Denmark., Heinzel C; Institute of Tropical Medicine, University Hospital Tübingen, Tübingen, Germany., Fendel R; Institute of Tropical Medicine, University Hospital Tübingen, Tübingen, Germany; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon; German Center for Infection Research, partner site Tübingen, Tübingen, Germany., Esen M; Institute of Tropical Medicine, University Hospital Tübingen, Tübingen, Germany; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon; German Center for Infection Research, partner site Tübingen, Tübingen, Germany., Kremsner PG; Institute of Tropical Medicine, University Hospital Tübingen, Tübingen, Germany; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon; German Center for Infection Research, partner site Tübingen, Tübingen, Germany., Ter Heine R; Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, Netherlands., Wertheim HF; Department of Medical Microbiology, Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands., Idorn M; Department of Biomedicine, Aarhus University, Aarhus, Denmark., Paludan SR; Department of Biomedicine, Aarhus University, Aarhus, Denmark., Underwood AP; Copenhagen Hepatitis C Program, Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Binderup A; Copenhagen Hepatitis C Program, Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Ramirez S; Copenhagen Hepatitis C Program, Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Bukh J; Copenhagen Hepatitis C Program, Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Soegaard M; ExpreS2ion Biotechnologies Aps, Hørsholm, Denmark., Erdogan SM; Centre for Medical Parasitology, Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Gustavsson T; Centre for Medical Parasitology, Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Clemmensen S; ExpreS2ion Biotechnologies Aps, Hørsholm, Denmark., Theander TG; Centre for Medical Parasitology, Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Salanti A; Centre for Medical Parasitology, Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Hamborg M; CMC Assist Aps, Copenhagen, Denmark., de Jongh WA; AdaptVac Aps, Copenhagen, Denmark., McCall MBB; Department of Medical Microbiology, Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands; Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands; Institute of Tropical Medicine, University Hospital Tübingen, Tübingen, Germany; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon., Nielsen MA; Centre for Medical Parasitology, Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: mortenn@sund.ku.dk., Mordmüller BG; Department of Medical Microbiology, Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands; Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands. Electronic address: benjamin.mordmueller@radboudumc.nl.
Jazyk:	angličtina
Zdroj:	The Lancet. Microbe [Lancet Microbe] 2023 Mar; Vol. 4 (3), pp. e140-e148. Date of Electronic Publication: 2023 Jan 18.
DOI:	10.1016/S2666-5247(22)00337-8
Abstrakt:	Background: Capsid virus-like particles (cVLP) have proven safe and immunogenic and can be a versatile platform to counter pandemics. We aimed to clinically test a modular cVLP COVID-19 vaccine in individuals who were naive to SARS-CoV-2. Methods: In this phase 1, single-centre, dose-escalation, adjuvant-selection, open-label clinical trial, we recruited participants at the Radboud University Medical Center in Nijmegen, Netherlands, and sequentially assigned them to seven groups. Eligible participants were healthy, aged 18-55 years, and tested negative for SARS-CoV-2 and anti-SARS-CoV-2 antibodies. Participants were vaccinated intramuscularly on days 0 and 28 with 6 μg, 12 μg, 25 μg, 50 μg, or 70 μg of the cVLP-based COVID-19 vaccine (ABNCoV2). A subgroup received MF59-adjuvanted ABNCoV2. Follow-up was for 24 weeks after second vaccination. The primary objectives were to assess the safety and tolerability of ABNCoV2 and to identify a dose that optimises the tolerability-immunogenicity ratio 14 days after the first vaccination. The primary safety endpoint was the number of related grade 3 adverse events and serious adverse events in the intention-to-treat population. The primary immunogenicity endpoint was the concentration of ABNCoV2-specific antibodies. The trial is registered with ClinicalTrials.gov, NCT04839146. Findings: 45 participants (six to nine per group) were enrolled between March 15 and July 15, 2021. Participants had a total of 249 at least possibly related solicited adverse events (185 grade 1, 63 grade 2, and one grade 3) within a week after vaccination. Two serious adverse events occurred; one was classified as a possible adverse reaction. Antibody titres were dose-dependent with levels plateauing at a vaccination dose of 25-70 μg ABNCoV2. After second vaccination, live virus neutralisation activity against major SARS-CoV-2 variants was high but was lower with an omicron (BA.1) variant. Vaccine-specific IFNγ + CD4 + T cells were induced. Interpretation: Immunisation with ABNCoV2 was well tolerated, safe, and resulted in a functional immune response. The data support the need for additional clinical development of ABNCoV2 as a second-generation SARS-CoV-2 vaccine. The modular cVLP platform will accelerate vaccine development, beyond SARS-CoV-2. Funding: EU, Carlsberg Foundation, and the Novo Nordisk Foundation. Competing Interests: Declaration of interests MAN, AFS, AS, TGT, and CJ are listed as coinventors on a patent application covering the AP205 CLP vaccine platform technology (WO2016112921 A1) licensed to AdaptVac. CF, AFS, and WAdJ are employees at AdaptVac, a company commercialising virus-like particle display technology and vaccines, including several patents. (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
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