2754. Phase 1 Trial of an mRNA-Based Combination Vaccine Against hMPV and PIV3

BACKGROUND: Human metapneumovirus (hMPV) and parainfluenza virus type 3 (PIV3) are important causes of upper and lower respiratory tract infections, particularly in young children. Despite their public health impact, no effective therapeutic or preventive options are available. mRNA-1653 is a mRNA-based investigational combination vaccine against hMPV and PIV3, and consists of two distinct mRNA sequences encoding the fusion proteins of hMPV and PIV3, co-formulated in lipid nanoparticles. METHODS: This phase 1, first-in-human, randomized, placebo-controlled, dose-ranging study assesses the safety and immunogenicity of mRNA-1653 in healthy adults aged 18–49. The 124-subject study evaluates four vaccine dose levels (25, 75, 150, and 300 µg) administered intramuscularly in either single-dose or two-dose (Day 1, Month 1) vaccination schedules, with follow-up through 1 year after the last vaccination. Objectives include safety and immunogenicity measured by hMPV- and PIV3-specific neutralizing antibody titers. RESULTS: An interim analysis demonstrated that the mRNA-1653 vaccine was generally well-tolerated at all dose levels. Neutralizing antibodies against hMPV and PIV3 were present at baseline in all subjects, consistent with prior exposure to both viruses. A single dose of mRNA-1653 boosted serum neutralization titers against both hMPV and PIV3, and the magnitude of boosting was similar at all dose levels. The geometric mean ratio of Month 1 to baseline titers was approximately 6 for hMPV and 3 for PIV3. A second dose of mRNA-1653 at Month 1 was not associated with further increase of hMPV or PIV3 neutralization titers. CONCLUSION: mRNA-1653 is well-tolerated and induces a functional immune response, and is therefore a promising vaccine candidate for the prevention of pediatric respiratory tract diseases caused by hMPV and PIV3. DISCLOSURES: All authors: No reported disclosures.