Safety and Immunogenicity of an mRNA-Based hMPV/PIV3 Combination Vaccine in Seropositive Children.

OBJECTIVES: Human metapneumovirus (hMPV) and parainfluenza virus type 3 (PIV3) are common respiratory illnesses in children. The safety and immunogenicity of an investigational mRNA-based vaccine, mRNA-1653, encoding membrane-anchored fusion proteins of hMPV and PIV3, was evaluated in hMPV/PIV3-seropositive children. METHODS: In this phase 1b randomized, observer-blind, placebo-controlled, dose-ranging study, hMPV/PIV3-seropositive children were enrolled sequentially into 2 dose levels of mRNA-1653 administered 2 months apart; children aged 12 to 36 months were randomized (1:1) to receive 10-µg of mRNA-1653 or placebo and children aged 12 to 59 months were randomized (3:1) to receive 30-µg of mRNA-1653 or placebo. RESULTS: Overall, 27 participants aged 18 to 55 months were randomized; 15 participants received 10-µg of mRNA-1653 (n = 8) or placebo (n = 7), whereas 12 participants received 30-µg of mRNA-1653 (n = 9) or placebo (n = 3). mRNA-1653 was well-tolerated at both dose levels. The only reported solicited local adverse reaction was tenderness at injection site; solicited systemic adverse reactions included grade 1 or 2 chills, irritability, loss of appetite, and sleepiness. A single 10-µg or 30-µg mRNA-1653 injection increased hMPV and PIV3 neutralizing antibody titers (geometric mean fold-rise ratio over baseline: hMPV-A = 2.9-6.1; hMPV-B = 6.2-13.2; PIV3 = 2.8-3.0) and preF and postF binding antibody concentrations (geometric mean fold-rise ratio: hMPV preF = 5.3-6.1; postF = 4.6-6.5 and PIV3 preF = 13.9-14.2; postF = 11.0-12.1); a second injection did not further increase antibody levels in these seropositive children. Binding antibody responses were generally preF biased. CONCLUSIONS: mRNA-1653 was well-tolerated and boosted hMPV and PIV3 antibody levels in seropositive children aged 12 to 59 months, supporting the continued development of mRNA-1653 or its components for the prevention of hMPV and PIV3.

Assessment of gait and balance impairment in people with spinocerebellar ataxia using wearable sensors.

OBJECTIVE: To explore the use of wearable sensors for objective measurement of motor impairment in spinocerebellar ataxia (SCA) patients during clinical assessments of gait and balance. METHODS: In total, 14 patients with genetically confirmed SCA (mean age 61.6 ± 8.6 years) and 4 healthy controls (mean age 49.0 ± 16.4 years) were recruited through the Massachusetts General Hospital (MGH) Ataxia Center. Participants donned seven inertial sensors while performing two independent trials of gait and balance assessments from the Scale for the Assessment and Rating of Ataxia (SARA) and Brief Ataxia Rating Scale (BARS2). Univariate analysis was used to identify sensor-derived metrics from wearable sensors that discriminate motor function between the SCA and control groups. Multivariate linear regression models were used to estimate the subjective in-person SARA/BARS2 ratings. Spearman correlation coefficients were used to evaluate the performance of the model. RESULTS: Stride length variability, stride duration, cadence, stance phase, pelvis sway, and turn duration were different between SCA and controls (p < 0.05). Similarly, sway and sway velocity of the ankle, hip, and center of mass differentiated SCA and controls (p < 0.05). Using these features, linear regression models showed moderate-to-strong correlation with clinical scores from the in-person rater during SARA assessments of gait (r = 0.73, p = 0.003) and stance (r = 0.90, p < 0.001) and the BARS2 gait assessment (r = 0.74, p = 0.003). CONCLUSION: This study demonstrates that sensor-derived metrics can potentially be used to estimate the level of motor impairment in patient with SCA quickly and objectively. Thus, digital biomarkers from wearable sensors have the potential to be an integral tool for SCA clinical trials and care.