Safety and Immunogenicity of an mRNA-Based Human Metapneumovirus and Parainfluenza Virus Type 3 Combined Vaccine in Healthy Adults

Abstract

Background: Human metapneumovirus (hMPV) and parainfluenza virus type 3 (PIV3) cause respiratory tract illness in children and the elderly. No licensed vaccines are available.

Methods: In this phase 1, randomized, dose-ranging, first-in-human study, the safety, reactogenicity, and humoral immunogenicity of an investigational mRNA-based hMPV and PIV3 combination vaccine, mRNA-1653, were evaluated in healthy adults aged 18-49 years. Sentinel participants (n = 20) received 2 doses of mRNA-1653 (25, 75, 150, or 300 μg) in the dose escalation phase, and participants (n = 104) received 2 doses of mRNA-1653 (75, 150, or 300 μg) or placebo in the dose selection phase; injections were 28 days apart.

Results: The most common solicited reactogenicity events were injection site pain, headache, fatigue, and myalgia, the majority of which were grade 1 or 2. A single mRNA-1653 dose increased neutralization titers against hMPV and PIV3 1 month after vaccination compared with baseline. No notable increases in neutralizing antibody titers were observed with escalating dose levels after mRNA-1653, although no statistical inferences were made; a second mRNA-1653 dose had little observable impact on antibody titers. Neutralizing titers through 1 year remained above baseline for hMPV and returned to baseline for PIV3.

Conclusions: mRNA-1653 was well tolerated, with an acceptable safety profile and increased hMPV and PIV3 neutralization titers in healthy adults.

Keywords: adult; human metapneumovirus; human parainfluenza virus; mRNA vaccine; parainfluenza virus type 3; safety and immunogenicity.

Figure 1.

Solicited local and systemic adverse events within 7 days of doses 1 and 2 (first vaccination and second vaccination solicited safety set^a). Solicited local (A) and systemic (B) adverse events presented by grade and treatment group following each dose. Dose 1, n = number of participants in the first vaccination solicited safety set; Dose 2, n = number of participants in the second vaccination solicited safety set. ^aAll participants in the exposed set with any solicited local or systemic reactogenicity events data after dose 1 or 2.

Figure 2.

GMRs and GMTs of serum neutralizing antibodies by dose level^a at baseline and month 1 for (A) hMPV-A, (B) hMPV-B, and (C) PIV3 (per-protocol immunogenicity set^b). ^aData are combined for the 1-dose and 2-dose mRNA-1653 groups at the 75-, 150-, and 300-μg dose levels.  ^bAll evaluable participants from the full analysis set who met all eligibility criteria, received study vaccination per protocol, did not receive a concomitant medication or vaccine leading to exclusion from analysis, did not present with a medical condition that might impact immunogenicity assessment, complied with the vaccination schedule and timing of the postvaccination blood sampling, and had ≥1 assay component for immune response evaluation at the respective time point (visit month 1). Abbreviations: BL, baseline; GMR, geometric mean ratio; GMT, geometric mean titer; hMPV, human metapneumovirus; PIV3, human parainfluenza virus type 3.  

Figure 3.

GMTs of serum neutralizing antibodies by vaccination group at baseline and months 1, 2, 7, and 13 for (A) hMPV-A, (B) hMPV-B, and (C) PIV3 (per-protocol immunogenicity set^a). ^aAll evaluable participants from the full analysis set who met all eligibility criteria, received study vaccination per protocol, did not receive a concomitant medication or vaccine leading to exclusion from analysis, did not present with a medical condition that might impact immunogenicity assessment, complied with the vaccination schedule and timing of the postvaccination blood sampling, and had ≥1 assay component for immune response evaluation at the respective time point (visit month 1, 2, 7, or 13). Abbreviations: BL, baseline; GMT, geometric mean titer; hMPV, human metapneumovirus; PIV3, human parainfluenza virus type 3.