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

• Main Authors: Brandon J. Essink (Author), Craig Shapiro (Author), Marie Grace Dawn Isidro (Author), Paul Bradley (Author), Antoinette Pragalos (Author), Mark Bloch (Author), Joel Santiaguel (Author), Melchor Victor Frias (Author), Spiros Miyakis (Author), Margarida Alves de Mesquita (Author), Stefano Berrè (Author), Charlotte Servais (Author), Natasha Waugh (Author), Claudia Hoffmann (Author), Emna Baba (Author), Oliver Schönborn-Kellenberger (Author), Olaf-Oliver Wolz (Author), Sven D. Koch (Author), Tapiwa Ganyani (Author), Philippe Boutet (Author), Philipp Mann (Author), Stefan O. Mueller (Author), Roshan Ramanathan (Author), Martin Robert Gaudinski (Author), Nicolas Vanhoutte (Author)
• Format: Book
• Published: Taylor & Francis Group, 2024-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.1080/21645515.2024.2408863; 2164-554X; 2164-5515
• Keywords: COVID-19; mRNA vaccine; booster; SARS-CoV-2 variants; safety; immunogenicity; Immunologic diseases. Allergy; RC581-607; Therapeutics. Pharmacology; RM1-950
• Source: Human Vaccines & Immunotherapeutics, Vol 20, Iss 1 (2024)

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.