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A fully liquid MenACWY-CRM vaccine presentation has been developed, modifying the meningococcal serogroup A (MenA) component from lyophilized to liquid. The safety and immunogenicity of the liquid presentation at the end of the intended shelf-life (aged for 24 or 30 months) were compared to the licensed lyophilized/liquid presentation. This multicenter, randomized (1:1), observer-blind, phase 2b study (NCT03433482) enrolled adolescents and young adults (age 10-40 years). In part 1, 844 participants received one dose of liquid presentation stored for approximately 24 months or licensed presentation. In part 2, 846 participants received one dose of liquid presentation stored for approximately 30 months or licensed presentation. After storage, the MenA free saccharide (FS) level was approximately 25% and O-acetylation was approximately 45%. The primary objective was to demonstrate non-inferiority of the liquid presentation to licensed presentation, as measured by human serum bactericidal assay (hSBA) geometric mean titers (GMTs) against MenA, 1-month post-vaccination. Immune responses against each vaccine serogroup were similar between groups. Between-group ratios of hSBA GMTs for MenA were 1.21 (part 1) and 1.11 (part 2), with two-sided 95% confidence interval lower limits (0.94 and 0.87, respectively) greater than the prespecified non-inferiority margin (0.5), thus meeting the primary study objective. No safety concerns were identified. Despite reduced O-acetylation of MenA and increased FS content, serogroup-specific immune responses induced by the fully liquid presentation were similar to those induced by the licensed MenACWY-CRM vaccine, with non-inferior anti-MenA responses. The safety profiles of the vaccine presentations were similar.

Simultaneous access to different biofluids enables an accurate analysis of multiple analytes, leading to a precision diagnosis and appropriate medication. Additionally, establishing a relationship between various markers in different biofluids and their correlation to biomarkers in blood allows the development of an algorithmic approach, which aids non-invasive diagnosis through single parameter monitoring. However, the main bottleneck that exists in multiple biofluid analyses for its clinical implementation is the requirement of an advanced microfluidic coupled device design, which empowers simultaneous collection and monitoring. To tackle this challenge, an epidermal wearable bio-fluidic patch that facilitates simultaneous on-demand extraction, sampling, and storage of sweat and interstitial fluid (ISF) together with monitoring of their corresponding counterions is presented. The clean room free development of a biofluidic patch is realized through 3D integration of laser patterned optimized microfluidic structures, a low-cost screen-printed stimulation module, and a potentiometric chloride (Cl - ) and calcium (Ca 2+ ) ion sensing module for adequate dual biofluid sampling and analysis. The developed Cl - and Ca 2+ ion-selective sensors exhibit good repeatability, selectivity, acceptable stability, and sensitivity. The proof-of-concept demonstration of the fabricated patch for simultaneous dual-sampling, storage, and monitoring of the sweat Cl - and ISF Ca 2+ on a healthy volunteer during different periods of the day leverages its potential in real-time personalized healthcare clinical usages. Furthermore, the patch's electronic interface and use of wireless transmission facilitates a point-of-care non-invasive lab-on-skin application for monitoring the health status of individuals.

Background: The currently licensed quadrivalent MenACWY-CRM conjugate vaccine presentation consists of two vials (lyophilised MenA and liquid MenCWY) to be reconstituted before injection. A new fully liquid formulation in a single vial has been developed to further improve the vaccine presentation. Since the MenA structure is subject to hydrolytic degradation, this study was conducted to compare the immunogenicity and safety of the investigational MenACWY-CRM liquid vaccine with the licensed vaccine., Methods: In this multicentre, randomised, controlled, observer-blind, phase 2b study, 979 healthy adults were administered a single dose of MenACWY-CRM liquid presentation or the currently licensed MenACWY-CRM vaccine. MenA free saccharide generation was accelerated to approximately 30% in the liquid presentation and MenA polysaccharide O-acetylation was reduced to approximately 40%, according to a controlled procedure. Immunological non-inferiority of the MenACWY-CRM liquid to the licensed vaccine, as measured by human serum bactericidal assay (hSBA) geometric mean titres (GMTs) against MenA 1 month post-vaccination, was the primary study objective. Safety assessment was among the secondary objectives., Results: Immune responses against each serogroup were similar between the two vaccine groups and was non-inferior for MenA. Adjusted hSBA GMTs for MenA were 185.16 and 211.33 for the MenACWY-CRM liquid presentation and currently licensed vaccine presentation, respectively. The between-group ratio of hSBA GMTs for MenA was 0.88, with a two-sided 95% confidence interval lower limit of 0.64, greater than the prespecified non-inferiority margin of 0.5, thus meeting the primary study objective. Both vaccines were well tolerated. No serious adverse events were considered related to vaccination., Conclusions: The levels of MenA free saccharide and polysaccharide O-acetylation did not affect the immunogenicity of the fully liquid presentation, which was demonstrated to be non-inferior to the immunogenicity of the currently licensed MenACWY-CRM vaccine against MenA. The immunogenicity, reactogenicity and safety profiles of the two vaccine presentations were similar., Competing Interests: Declaration of Competing Interest TA, SVH, MA, BK, BdW, GFDD, MC, PVS, EF, ML and MP are employed by the GSK group of companies. TA, MA, BdW, PVS, EF, ML and MP hold shares in the GSK group of companies. CV reports her institution received payments from the GSK group of companies, MSD and Pfizer, outside the submitted work. ILR reports her institution received payments from the GSK group of companies for the conduct of the study. TN reports payments from the GSK group of companies, Merck, Sanofi Pasteur and Seqirus, outside the submitted work. TA, SVH, MA, BK, BdW, GFDD, MC, PVS, EF, ML, MP, CV, ILR and TN declare no other financial and non-financial relationships and activities. JV, TS, GG, MF, GI, TFS, AMN and SC declare no financial and non-financial relationships and activities and no conflicts of interest., (Copyright © 2021 GlaxoSmithKline Biologicals S.A. Published by Elsevier Ltd.. All rights reserved.)