Safety and immunogenicity of a modified mRNA-lipid nanoparticle vaccine candidate against COVID-19: Results from a phase 1, dose-escalation study

This phase 1, open-label, dose-escalation, multi-center study (NCT05477186) assessed the safety and immunogenicity of a booster dose of an mRNA COVID-19 vaccine (CV0501) encoding the SARS-CoV-2 Omicron BA.1 spike protein. Participants aged ≥ 18 years previously vaccinated with ≥ 2 doses of an mRNA C...

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Main Authors: Brandon J. Essink, Craig Shapiro, Marie Grace Dawn Isidro, Paul Bradley, Antoinette Pragalos, Mark Bloch, Joel Santiaguel, Melchor Victor Frias, Spiros Miyakis, Margarida Alves de Mesquita, Stefano Berrè, Charlotte Servais, Natasha Waugh, Claudia Hoffmann, Emna Baba, Oliver Schönborn-Kellenberger, Olaf-Oliver Wolz, Sven D. Koch, Tapiwa Ganyani, Philippe Boutet, Philipp Mann, Stefan O. Mueller, Roshan Ramanathan, Martin Robert Gaudinski, Nicolas Vanhoutte
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Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Human Vaccines & Immunotherapeutics
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Online Access:https://www.tandfonline.com/doi/10.1080/21645515.2024.2408863
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author Brandon J. Essink
Craig Shapiro
Marie Grace Dawn Isidro
Paul Bradley
Antoinette Pragalos
Mark Bloch
Joel Santiaguel
Melchor Victor Frias
Spiros Miyakis
Margarida Alves de Mesquita
Stefano Berrè
Charlotte Servais
Natasha Waugh
Claudia Hoffmann
Emna Baba
Oliver Schönborn-Kellenberger
Olaf-Oliver Wolz
Sven D. Koch
Tapiwa Ganyani
Philippe Boutet
Philipp Mann
Stefan O. Mueller
Roshan Ramanathan
Martin Robert Gaudinski
Nicolas Vanhoutte
author_facet Brandon J. Essink
Craig Shapiro
Marie Grace Dawn Isidro
Paul Bradley
Antoinette Pragalos
Mark Bloch
Joel Santiaguel
Melchor Victor Frias
Spiros Miyakis
Margarida Alves de Mesquita
Stefano Berrè
Charlotte Servais
Natasha Waugh
Claudia Hoffmann
Emna Baba
Oliver Schönborn-Kellenberger
Olaf-Oliver Wolz
Sven D. Koch
Tapiwa Ganyani
Philippe Boutet
Philipp Mann
Stefan O. Mueller
Roshan Ramanathan
Martin Robert Gaudinski
Nicolas Vanhoutte
author_sort Brandon J. Essink
collection DOAJ
description This phase 1, open-label, dose-escalation, multi-center study (NCT05477186) assessed the safety and immunogenicity of a booster dose of an mRNA COVID-19 vaccine (CV0501) encoding the SARS-CoV-2 Omicron BA.1 spike protein. Participants aged ≥ 18 years previously vaccinated with ≥ 2 doses of an mRNA COVID-19 vaccine received CV0501 doses ranging from 12 to 200 μg. After assessment of safety and immunogenicity of the 12 μg dose in 30 adults, 30 adults ≤ 64 years were randomized to receive either a 3 or 6 μg dose. Solicited adverse events (AEs) were collected for 7 days, unsolicited AEs for 28 days, and serious AEs (SAEs), medically attended AEs (MAAEs), and AEs of special interest (AESIs) until day (D) 181 post-vaccination. Serum neutralizing titers specific to SARS-CoV-2 BA.1, wild-type, Delta, and additional Omicron subvariants were assessed at D1, D15, D29, D91, and D181. Of 180 vaccinated participants (mean age: 49.3 years; 57.8% women), 70.6% had prior SARS-CoV-2 infection. Most solicited local (98.1%) and systemic (96.7%) AEs were of mild-to-moderate severity; the most common were injection site pain (57.5%; 33.3–73.3% across groups) and myalgia (36.9%; 13.3–56.7%). Unsolicited AEs were reported by 14.4% (6.7–26.7%) of participants (mild-to-moderate severity in 88.5% of the participants). Three participants (1.7%) reported SAEs, 16.7% (6.7–30.0%) reported MAAEs, and 8.3% (0.0–13.3%) reported AESIs (15 COVID-19 cases), none related to vaccination. Geometric means of serum neutralizing titers increased from baseline to D15 and D29 (dose-dependent), and then decreased over time. The safety and immunogenicity results supported advancement to a phase 2 trial.
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spelling doaj-art-b801d4c67eeb429f80a7051c7f35eae62025-08-20T02:16:44ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2024-12-0120110.1080/21645515.2024.2408863Safety and immunogenicity of a modified mRNA-lipid nanoparticle vaccine candidate against COVID-19: Results from a phase 1, dose-escalation studyBrandon J. Essink0Craig Shapiro1Marie Grace Dawn Isidro2Paul Bradley3Antoinette Pragalos4Mark Bloch5Joel Santiaguel6Melchor Victor Frias7Spiros Miyakis8Margarida Alves de Mesquita9Stefano Berrè10Charlotte Servais11Natasha Waugh12Claudia Hoffmann13Emna Baba14Oliver Schönborn-Kellenberger15Olaf-Oliver Wolz16Sven D. Koch17Tapiwa Ganyani18Philippe Boutet19Philipp Mann20Stefan O. Mueller21Roshan Ramanathan22Martin Robert Gaudinski23Nicolas Vanhoutte24Velocity Clinical Research, Omaha, NE, USACenExel RCA, Hollywood, FL, USAWest Visayas State University, Iloilo, PhilippinesVelocity Clinical Research, Savannah, GA, USACTI Clinical Research Center, Cincinnati, OH, USAHoldsworth House Medical Practice Sydney, Darlinghurst, New South Wales, AustraliaQuirino Memorial Medical Center, Quezon, PhilippinesDe La Salle Medical and Health Sciences Institute, Dasmariñas, Cavite, PhilippinesWollongong Hospital, Wollongong, New South Wales, AustraliaCureVac SE, Wiesbaden, GermanyGSK, Rixensart, BelgiumGSK, Rixensart, BelgiumGSK, Brentford, Middlesex, UKCureVac SE, Wiesbaden, GermanyGSK, Wavre, BelgiumCureVac SE, Wiesbaden, GermanyCureVac SE, Tübingen, GermanyCureVac SE, Tübingen, GermanyGSK, Wavre, BelgiumGSK, Rixensart, BelgiumCureVac SE, Wiesbaden, GermanyCureVac SE, Tübingen, GermanyGSK, Rockville, MD, USAGSK, Rockville, MD, USAGSK, Wavre, BelgiumThis phase 1, open-label, dose-escalation, multi-center study (NCT05477186) assessed the safety and immunogenicity of a booster dose of an mRNA COVID-19 vaccine (CV0501) encoding the SARS-CoV-2 Omicron BA.1 spike protein. Participants aged ≥ 18 years previously vaccinated with ≥ 2 doses of an mRNA COVID-19 vaccine received CV0501 doses ranging from 12 to 200 μg. After assessment of safety and immunogenicity of the 12 μg dose in 30 adults, 30 adults ≤ 64 years were randomized to receive either a 3 or 6 μg dose. Solicited adverse events (AEs) were collected for 7 days, unsolicited AEs for 28 days, and serious AEs (SAEs), medically attended AEs (MAAEs), and AEs of special interest (AESIs) until day (D) 181 post-vaccination. Serum neutralizing titers specific to SARS-CoV-2 BA.1, wild-type, Delta, and additional Omicron subvariants were assessed at D1, D15, D29, D91, and D181. Of 180 vaccinated participants (mean age: 49.3 years; 57.8% women), 70.6% had prior SARS-CoV-2 infection. Most solicited local (98.1%) and systemic (96.7%) AEs were of mild-to-moderate severity; the most common were injection site pain (57.5%; 33.3–73.3% across groups) and myalgia (36.9%; 13.3–56.7%). Unsolicited AEs were reported by 14.4% (6.7–26.7%) of participants (mild-to-moderate severity in 88.5% of the participants). Three participants (1.7%) reported SAEs, 16.7% (6.7–30.0%) reported MAAEs, and 8.3% (0.0–13.3%) reported AESIs (15 COVID-19 cases), none related to vaccination. Geometric means of serum neutralizing titers increased from baseline to D15 and D29 (dose-dependent), and then decreased over time. The safety and immunogenicity results supported advancement to a phase 2 trial.https://www.tandfonline.com/doi/10.1080/21645515.2024.2408863COVID-19mRNA vaccineboosterSARS-CoV-2 variantssafetyimmunogenicity
spellingShingle Brandon J. Essink
Craig Shapiro
Marie Grace Dawn Isidro
Paul Bradley
Antoinette Pragalos
Mark Bloch
Joel Santiaguel
Melchor Victor Frias
Spiros Miyakis
Margarida Alves de Mesquita
Stefano Berrè
Charlotte Servais
Natasha Waugh
Claudia Hoffmann
Emna Baba
Oliver Schönborn-Kellenberger
Olaf-Oliver Wolz
Sven D. Koch
Tapiwa Ganyani
Philippe Boutet
Philipp Mann
Stefan O. Mueller
Roshan Ramanathan
Martin Robert Gaudinski
Nicolas Vanhoutte
Safety and immunogenicity of a modified mRNA-lipid nanoparticle vaccine candidate against COVID-19: Results from a phase 1, dose-escalation study
Human Vaccines & Immunotherapeutics
COVID-19
mRNA vaccine
booster
SARS-CoV-2 variants
safety
immunogenicity
title Safety and immunogenicity of a modified mRNA-lipid nanoparticle vaccine candidate against COVID-19: Results from a phase 1, dose-escalation study
title_full Safety and immunogenicity of a modified mRNA-lipid nanoparticle vaccine candidate against COVID-19: Results from a phase 1, dose-escalation study
title_fullStr Safety and immunogenicity of a modified mRNA-lipid nanoparticle vaccine candidate against COVID-19: Results from a phase 1, dose-escalation study
title_full_unstemmed Safety and immunogenicity of a modified mRNA-lipid nanoparticle vaccine candidate against COVID-19: Results from a phase 1, dose-escalation study
title_short Safety and immunogenicity of a modified mRNA-lipid nanoparticle vaccine candidate against COVID-19: Results from a phase 1, dose-escalation study
title_sort safety and immunogenicity of a modified mrna lipid nanoparticle vaccine candidate against covid 19 results from a phase 1 dose escalation study
topic COVID-19
mRNA vaccine
booster
SARS-CoV-2 variants
safety
immunogenicity
url https://www.tandfonline.com/doi/10.1080/21645515.2024.2408863
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