ABSTRACT
BACKGROUND: We evaluated co-administration of adjuvanted seasonal quadrivalent influenza vaccine (FLU-aQIV) and respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVPreF3 OA) in ≥65-year-olds. METHODS: This phase 3, open-label trial randomized ≥65-year-olds to receive FLU-aQIV and RSVPreF3 OA concomitantly (Co-Ad) or sequentially, 1 month apart (Control). Primary objectives were to demonstrate the non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration in terms of hemagglutination inhibition (HI) titers for each FLU-aQIV strain and RSV-A and RSV-B neutralization titers, 1 month post-vaccination. Reactogenicity and safety were also assessed. RESULTS: Overall, 1045 participants were vaccinated (Co-Ad: 523; Control: 522). Non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration was demonstrated in terms of HI titers for the A/Victoria(H1N1), B/Victoria, and B/Yamagata influenza strains and RSV-A neutralization titers (upper limits [ULs] of 95% confidence intervals [CIs] for adjusted geometric mean titer [GMT] ratios [Control/Co-Ad] ≤1.50) but not for A/Darwin(H3N2) HI titers (95% CI UL = 1.53). The immune response to A/Darwin(H3N2) was further assessed post-hoc using a microneutralization assay; the post-vaccination adjusted GMT ratio (Control/Co-Ad) was 1.23 (95% CI: 1.06-1.42, ie, UL ≤1.50), suggesting an adequate immune response to A/Darwin(H3N2) following co-administration. RSV-B neutralization titers were comparable between groups (95% CI UL for adjusted GMT ratio ≤1.50). Solicited adverse events were mostly mild or moderate and transient; unsolicited and serious adverse event rates were balanced between groups. CONCLUSIONS: Adjuvanted FLU-aQIV and RSVPreF3 OA had acceptable reactogenicity/safety profiles when co-administered in ≥65-year-olds, without clinically relevant interference with the immune responses to either vaccine. CLINICAL TRIALS REGISTRATION: NCT05568797.
ABSTRACT
Animal venoms are considered sterile sources of antimicrobial compounds with strong membrane-disrupting activity against multidrug-resistant bacteria. However, venomous bite wound infections are common in developing nations. Investigating the envenomation organ and venom microbiota of five snake and two spider species, we observed venom community structures that depend on the host venomous animal species and evidenced recovery of viable microorganisms from black-necked spitting cobra (Naja nigricollis) and Indian ornamental tarantula (Poecilotheria regalis) venoms. Among the bacterial isolates recovered from N. nigricollis, we identified two venom-resistant, novel sequence types of Enterococcus faecalis whose genomes feature 16 virulence genes, indicating infectious potential, and 45 additional genes, nearly half of which improve bacterial membrane integrity. Our findings challenge the dogma of venom sterility and indicate an increased primary infection risk in the clinical management of venomous animal bite wounds. IMPORTANCE Notwithstanding their 3 to 5% mortality, the 2.7 million envenomation-related injuries occurring annually-predominantly across Africa, Asia, and Latin America-are also major causes of morbidity. Venom toxin-damaged tissue will develop infections in some 75% of envenomation victims, with E. faecalis being a common culprit of disease; however, such infections are generally considered to be independent of envenomation. Here, we provide evidence on venom microbiota across snakes and arachnida and report on the convergent evolution mechanisms that can facilitate adaptation to black-necked cobra venom in two independent E. faecalis strains, easily misidentified by biochemical diagnostics. Therefore, since inoculation with viable and virulence gene-harboring bacteria can occur during envenomation, acute infection risk management following envenomation is warranted, particularly for immunocompromised and malnourished victims in resource-limited settings. These results shed light on how bacteria evolve for survival in one of the most extreme environments on Earth and how venomous bites must be also treated for infections.
Subject(s)
Arachnida , Venoms , Animals , Asia , Bacteria/genetics , SnakesABSTRACT
Holographic sensors are two-dimensional (2D) photonic crystals that diffract narrow-band light in the visible spectrum to quantify analytes in aqueous solutions. Here, a holographic fabrication setup was developed to produce holographic sensors through a doubly polymerization system of a poly-2-hydroxyethyl methacrylate hydrogel film using a pulsed Nd:YAG laser (λ = 355 nm, 5 ns, 100 mJ). Wavelength shifts of holographic Bragg peak in response to alcohol species (0-100 vol %) were characterized. Diffraction spectra showed that the holographic sensors could be used for short-chain alcohols at concentrations up to 60 vol %. The reversibility of the sensor was demonstrated, exhibiting a response time of 7.5 min for signal saturation. After 30 cycles, the Bragg peak and color remained the same in both 20 and 60 vol %. The fabrication parameters were simulated in MATLAB using a 2D finite-difference time-domain algorithm to model the interference pattern and energy flux profile of laser beam recording in the hydrogel medium. This work demonstrates a particle-free holographic sensor that offers continuous, reversible, and rapid colorimetric readouts for the real-time quantification of alcohols.
Subject(s)
Holography , Colorimetry , Hydrogels , Optics and Photonics , PhotonsABSTRACT
We assessed racial disparities in policing in the United States by compiling and analysing a dataset detailing nearly 100 million traffic stops conducted across the country. We found that black drivers were less likely to be stopped after sunset, when a 'veil of darkness' masks one's race, suggesting bias in stop decisions. Furthermore, by examining the rate at which stopped drivers were searched and the likelihood that searches turned up contraband, we found evidence that the bar for searching black and Hispanic drivers was lower than that for searching white drivers. Finally, we found that legalization of recreational marijuana reduced the number of searches of white, black and Hispanic drivers-but the bar for searching black and Hispanic drivers was still lower than that for white drivers post-legalization. Our results indicate that police stops and search decisions suffer from persistent racial bias and point to the value of policy interventions to mitigate these disparities.