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Hum Vaccin Immunother . Safety and immunogenicity of a modified mRNA-lipid nanoparticle vaccine candidate against COVID-19: Results from a phase 1,

tetano

Editor, Senior Moderator
Hum Vaccin Immunother


. 2024 Dec 31;20(1):2408863.
doi: 10.1080/21645515.2024.2408863. Epub 2024 Oct 18. Safety and immunogenicity of a modified mRNA-lipid nanoparticle vaccine candidate against COVID-19: Results from a phase 1, dose-escalation study

Brandon J Essink[SUP] 1 [/SUP], Craig Shapiro[SUP] 2 [/SUP], Marie Grace Dawn Isidro[SUP] 3 [/SUP], Paul Bradley[SUP] 4 [/SUP], Antoinette Pragalos[SUP] 5 [/SUP], Mark Bloch[SUP] 6 [/SUP], Joel Santiaguel[SUP] 7 8 [/SUP], Melchor Victor Frias[SUP] 9 [/SUP], Spiros Miyakis[SUP] 10 11 [/SUP], Margarida Alves de Mesquita[SUP] 12 [/SUP], Stefano Berrè[SUP] 13 [/SUP], Charlotte Servais[SUP] 13 [/SUP], Natasha Waugh[SUP] 14 [/SUP], Claudia Hoffmann[SUP] 12 [/SUP], Emna Baba[SUP] 15 [/SUP], Oliver Schönborn-Kellenberger[SUP] 12 [/SUP], Olaf-Oliver Wolz[SUP] 16 [/SUP], Sven D Koch[SUP] 16 [/SUP], Tapiwa Ganyani[SUP] 15 [/SUP], Philippe Boutet[SUP] 13 [/SUP], Philipp Mann[SUP] 12 [/SUP], Stefan O Mueller[SUP] 16 [/SUP], Roshan Ramanathan[SUP] 17 [/SUP], Martin Robert Gaudinski[SUP] 17 [/SUP], Nicolas Vanhoutte[SUP] 15 [/SUP]



Affiliations
Abstract

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.

Keywords: COVID-19; SARS-CoV-2 variants; booster; clinical trial; immunogenicity; mRNA vaccine; safety.

 
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