Safety, Tolerability, and Immunogenicity of an mRNA-Based Respiratory Syncytial Virus Vaccine in Healthy Young Adults in a Phase 1 Clinical Trial

• Published in: The Journal of infectious diseases 2024-09, Vol.230 (3), p.e637-e646
• Main Authors: Shaw, Christine A, Mithani, Runa, Kapoor, Archana, Dhar, Rakesh, Wilson, Lauren, El Asmar, Laila, Schnyder-Ghamloush, Sabine, Schaefers, Kristi, August, Allison, Stoszek, Sonia K, Chen, Grace L
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Antibodies; Antibodies, Neutralizing - blood; Antibodies, Neutralizing - immunology; Antibodies, Viral - blood; Antibody response; Clinical trials; Female; Healthy Volunteers; Humans; Immunogenicity; Immunogenicity, Vaccine; Major; Male; Middle Aged; mRNA; mRNA Vaccines; Myalgia; Nanoparticles; Nanoparticles - administration & dosage; Placebos; Public health; Respiratory syncytial virus; Respiratory Syncytial Virus Infections - immunology; Respiratory Syncytial Virus Infections - prevention & control; Respiratory Syncytial Virus Vaccines - administration & dosage; Respiratory Syncytial Virus Vaccines - adverse effects; Respiratory Syncytial Virus Vaccines - genetics; Respiratory Syncytial Virus Vaccines - immunology; Respiratory Syncytial Virus, Human - genetics; Respiratory Syncytial Virus, Human - immunology; RNA, Messenger - genetics; RNA, Messenger - immunology; Vaccines; Young Adult; Young adults
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiae035

Abstract Background Respiratory syncytial virus (RSV) presents a global health concern. A lipid nanoparticle–encapsulated mRNA-based RSV vaccine (mRNA-1345) that encodes the membrane-anchored RSV prefusion–stabilized F glycoprotein is under clinical investigation. Methods This phase 1 dose escalation study was based on a randomized, observer-blind, placebo-controlled design, and it assessed the safety and immunogenicity of mRNA-1345 in healthy adults aged 18 to 49 years. Participants were randomized to receive 1 dose of mRNA-1345 (50, 100, or 200 µg) or placebo or 3 doses of mRNA-1345 (100 µg) or placebo 56 days apart. Results mRNA-1345 was well tolerated at all dose levels. The most common solicited adverse reactions were pain, headache, fatigue, myalgia, or chills, which were all generally mild to moderate. At 1 month postinjection, a single injection of mRNA-1345 boosted RSV neutralizing antibody titers (geometric mean fold rise: RSV-A, 20.0–23.5; RSV-B, 11.7–16.0) and RSV prefusion binding antibody concentrations (geometric mean fold rise, 16.1–21.8), with no apparent dose response. Antibody levels remained above baseline through 6 months. Sequential doses of 100 µg were well tolerated but did not further boost antibody levels. Conclusions A single mRNA-1345 injection demonstrated an acceptable safety profile in younger adults and induced a durable neutralizing antibody response, supporting its continued development. Clinical Trials Registration ClinicalTrials.gov NCT04528719. Respiratory syncytial virus presents a global health concern. We assessed the safety and immunogenicity of an mRNA-based vaccine, mRNA-1345, in healthy adults aged 18 to 49 years. mRNA-1345 vaccine was well tolerated and immunogenic in younger adults.