Safety, immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine: pooled phase 1, 2, 3a and 3b randomized, controlled trials.

Combination of waning immunity and lower effectiveness against new SARS-CoV-2 variants of approved COVID-19 vaccines necessitates new vaccines. We evaluated two doses, 28 days apart, of ARCT-154, a self-amplifying mRNA COVID-19 vaccine, compared with saline placebo in an integrated phase 1/2/3a/3b controlled, observer-blind trial in Vietnamese adults (ClinicalTrial.gov identifier: NCT05012943). Primary safety and reactogenicity outcomes were unsolicited adverse events (AE) 28 days after each dose, solicited local and systemic AE 7 days after each dose, and serious AEs throughout the study. Primary immunogenicity outcome was the immune response as neutralizing antibodies 28 days after the second dose. Efficacy against COVID-19 was assessed as primary and secondary outcomes in phase 3b. ARCT-154 was well tolerated with generally mild-moderate transient AEs. Four weeks after the second dose 94.1% (95% CI: 92.1-95.8) of vaccinees seroconverted for neutralizing antibodies, with a geometric mean-fold rise from baseline of 14.5 (95% CI: 13.6-15.5). Of 640 cases of confirmed COVID-19 eligible for efficacy analysis most were due to the Delta (B.1.617.2) variant. Efficacy of ARCT-154 was 56.6% (95% CI: 48.7- 63.3) against any COVID-19, and 95.3% (80.5-98.9) against severe COVID-19. ARCT-154 vaccination is well tolerated, immunogenic and efficacious, particularly against severe COVID-19 disease.

Optimising metameric spectra for integrative lighting to modulate the circadian system without affecting visual appearance.

Smart integrative lighting systems aim to support human health and wellbeing by capitalising on the light-induced effects on circadian rhythms, sleep, and cognitive functions, while optimising the light's visual aspects like colour fidelity, visual comfort, visual preference, and visibility. Metameric spectral tuning could be an instrument to solve potential conflicts between the visual preferences of users with respect to illuminance and chromaticity and the circadian consequences of the light exposure, as metamers can selectively modulate melanopsin-based photoreception without affecting visual properties such as chromaticity or illuminance. This work uses a 6-, 8- and 11-channel LED luminaire with fixed illuminance of 250 lx to systematically investigate the metameric tuning range in melanopic equivalent daylight illuminance (EDI) and melanopic daylight efficacy ratio (melanopic DER) for 561 chromaticity coordinates as optimisation targets (2700 K to 7443 K ± Duv 0 to 0.048), while applying colour fidelity index Rf criteria from the TM-30-20 Annex E recommendations (i.e. Rf [Formula: see text] 85, Rf,h1 [Formula: see text] 85). Our results reveal that the melanopic tuning range increases with rising CCT to a maximum tuning range in melanopic DER of 0.24 (CCT: 6702 K, Duv: 0.003), 0.29 (CCT: 7443 K, Duv: 0) and 0.30 (CCT: 6702, Duv: 0.006), depending on the luminaire's channel number of 6, 8 or 11, respectively. This allows to vary the melanopic EDI from 212.5-227.5 lx up to 275-300 lx without changes in the photopic illuminance (250 lx) or chromaticity ([Formula: see text] [Formula: see text] 0.0014). The highest metameric melanopic Michelson contrast for the 6-, 8- and 11-channel luminaire is 0.16, 0.18 and 0.18, which is accomplished at a CCT of 3017 K (Duv: - 0.018), 3456 K (Duv: 0.009) and 3456 K (Duv: 0.009), respectively. By optimising ~ 490,000 multi-channel LED spectra, we identified chromaticity regions in the CIExy colour space that are of particular interest to control the melanopic efficacy with metameric spectral tuning.