TY - JOUR
T1 - First-in-human use of a modular capsid virus-like vaccine platform
T2 - an open-label, non-randomised, phase 1 clinical trial of the SARS-CoV-2 vaccine ABNCoV2
AU - Smit, Merel J
AU - Sander, Adam F
AU - Ariaans, Maud B P A
AU - Fougeroux, Cyrielle
AU - Heinzel, Constanze
AU - Fendel, Rolf
AU - Esen, Meral
AU - Kremsner, Peter G
AU - Ter Heine, Rob
AU - Wertheim, Heiman F
AU - Idorn, Manja
AU - Paludan, Søren Riis
AU - Underwood, Alexander P
AU - Binderup, Alekxander
AU - Ramirez, Santseharay
AU - Bukh, Jens
AU - Soegaard, Max
AU - Erdogan, Sayit M
AU - Gustavsson, Tobias
AU - Clemmensen, Stine
AU - Theander, Thor G
AU - Salanti, Ali
AU - Hamborg, Mette
AU - de Jongh, Willem A
AU - McCall, Matthew B B
AU - Nielsen, Morten A
AU - Mordmüller, Benjamin G
AU - COUGH-1 trial study group
N1 - 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.
PY - 2023/3
Y1 - 2023/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85153968892&partnerID=8YFLogxK
U2 - 10.1016/S2666-5247(22)00337-8
DO - 10.1016/S2666-5247(22)00337-8
M3 - Journal article
C2 - 36681093
SN - 2666-5247
VL - 4
SP - e140-e148
JO - The Lancet. Microbe
JF - The Lancet. Microbe
IS - 3
ER -